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How do viroids and virusoids cause infection to a specific host ? How could they indentify the host without protein?

How do viroids and virusoids cause infection to a specific host ? How could they indentify the host without protein?


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We know, the capsule provides specific pathogenecity for the virus right ? Then , how do viroids and virusoids cause infection to a specific host ? How could they indentify the host without protein ? Seems like they could infect any possible living being ? Please make it clear


Small RNA derived from Tobacco mosaic virus targets a host C2-domain abscisic acid-related (CAR) 7-like protein gene

Tobacco mosaic virus (TMV) is a positive-sense single-stranded RNA virus. The 3′ end of TMV genome is consisted of an upstream pseudoknot domain (UPD) and a tRNA-like structure (TLS), both of which are important RNA elements to enhance TMV replication and translation. Deep-sequencing analysis revealed that TMV-specific viral small interfering RNAs (vsiRNAs) were generated in TMV-infected Nicotiana benthamiana plants. A vsiRNA derived from the juxtaposition between UPD and TLS, named TMV-vsiRNA 22 nt (6285–6306), possessed high sequence complementarity to a host gene which encodes a C2-domain abscisic acid (ABA)-related (CAR) 7-like protein. CAR proteins play a critical role in ABA signaling pathway. The CAR protein-encoding gene was amplified from N. benthamiana leaves and termed as Nb-CAR7. In TMV-infected plants, accumulation of Nb-CAR7 transcripts was significantly decreased, as compared with that of mock-inoculated and TMV-43A-infected plants. TMV-43A is a mutant without the UPD sequence in its genome. Overexpression of Nb-CAR7 led to decreased TMV RNA accumulation in the TMV-inoculated leaves. Silencing of Nb-CAR7 enhanced TMV replication and resulted in a higher viral RNA accumulation. In addition, the expression level of Nb-CAR7 was positively correlated to that of a low-temperature-induced ABA responsive gene (LTI65). The effect of Nb-CAR7 on TMV RNA accumulation in host plants was linked to ABA signaling pathway. In conclusion, a vsiRNA derived from the juxtaposition between UPD and TLS at the 3′UTR of TMV targets a host CAR7 gene.


Introduction

Mechanisms of gene regulation have long been studied and illustrated mostly at the level of individual cells. With increasing findings of cell-to-cell and long-distance trafficking of RNAs and proteins, some of which have been shown to regulate plant development, mechanisms of gene regulation including final cellular destination of certain gene products must now be considered at the whole plant level ( Lucas and Lee 2004 Lough and Lucas 2006 Ding and Itaya 2007a Kehr and Buhtz 2008 Lucas et al. 2009 Turgeon and Wolf 2009 ). Besides its role in plant developmental processes, cell-to-cell and/or long-distance trafficking of RNA molecules and/or proteins is crucial to the establishment of systemic infection by viruses and viroids ( Boevink and Oparka 2005 Flores et al. 2005 Scholthof 2005 Lucas 2006 Taliansky et al. 2008 Tsagris et al. 2008 Ding 2009 ) and to systemic plant defense responses ( Ding and Voinnet 2007 Díaz-Pendón and Ding 2008 Kalantidis et al. 2008 ). The study of how gene expression and metabolism in individual cells within a plant are integrated, through RNA and protein trafficking, to enable development, internal function and response to the environment is rapidly emerging as a new frontier of plant biology.

The plasmodesmata and phloem form a symplasmic network of channels for cell-to-cell and long-distance trafficking of RNAs, proteins, viruses, viroids as well as photoassimilates from sources where they are generated to various sink organs (Figure 1). This review addresses cell-to-cell and long-distance trafficking of RNA, with a focus on the use of viroids as models to probe mechanistic and evolutionary questions. Mechanisms and functions of cellular RNA trafficking are covered by Hannapel in this special issue ( Hannapel 2010 ). Here, we first briefly summarize examples of RNA trafficking to show its importance and then devote most of the discussion on research findings from viroids that have contributed to advance our understanding of the trafficking mechanisms. We further use viroid examples to illustrate the potentially enormous diversity of trafficking machinery plants have evolved and the great promise for new discoveries for the coming years. Finally, we discuss the prospect of integrating findings from different experimental systems to achieve a systems-based understanding of RNA trafficking function, mechanism and evolution.

Conceptualized integration of cell-to-cell and long-distance symplasmic transport pathways for proteins, RNAs, viruses, viroids as well as photoassimilates within a plant body. (A) Molecules generated within a source leaf that are destined to remote sink organs are transported through plasmodesmata across various cell layers (blue arrows cell layers are not illustrated for simplicity) to enter the phloem for long-distance transport to the sink organs (red arrows). (B) Schematic of a plasmodesma that comprises the plasma membrane (PM) surrounding a cylinder of modified endoplasmic reticulum (ER) that create a cytoplasmic connection between two neighboring cells. The cytoplasmic sleeve (CS) forms microchannels for intercellular transport. (C) An idealized vascular bundle in which a layer of bundle sheath encloses the xylem, identified by the tracheary elements, and phloem, identified by the sieve elements and companion cells. The sieve elements are interconnected end to end to form sieve tubes for transport.


Introduction

Studies on viroids have led to the discovery of some of the most interesting principles of the biology of RNA: the fact that a non-coding, non-translatable RNA can cause a disease ( Diener, 1971 ), the extraordinary small size of their genome ( Gross et al., 1978 ) and their circularity ( Sänger et al., 1976 ), which enables them to circumvent the problems of linear genome replication such as the accurate replication of linear ends ( Diener, 1989 ). One of the first self-cleaving structures, the hammerhead ribozyme, was found in a satellite RNA virus and a viroid RNA ( Prody et al., 1986 Forster and Symons, 1987 Forster et al., 1987 ). Prior to the molecular characterization of the hepatitis delta virus (HDV), a circular (‘viroid-like’) RNA infecting human liver cells and associated with hepatitis B virus ( Lai, 2005 Taylor, 2006 ) viroids remained as an interesting, but exotic example of a plant pathogen, investigated by some researchers in the field of plant pathology and molecular plant virology, together with a group of biophysicists studying RNA structure. They recognized in this relatively abundant, natural RNA a perfect object to study RNA structure transitions. Viroids have been the basis on which new experimental and computational methods have been developed ( Riesner, 1991 Steger and Riesner, 2003 ). A recent landmark of scientific breakthrough originating from viroid research is the discovery of RNA-mediated de novo DNA methylation, which was first described in transgenic plants carrying copies of the viroid cDNA ( Wassenegger et al., 1994 ). Although this was an ‘artificial’ transgenic system, it was quickly recognized that RNA-mediated DNA methylation is a mechanism that is a part of a whole battery of responses that plants have towards environmental changes and developmental programmes ( Wassenegger, 2005 Henderson and Jacobsen, 2007 ).

Several reviews have been published recently on viroids, showing the increasing scientific interest in these molecules as a model system and plant pathogen. In this review, we will discuss some of the most recent articles on viroids, and present some possible models concerning their replication, biogenesis and evolution.


15.1 Characteristics of Infectious Disease

Michael, a 10-year-old boy in generally good health, went to a birthday party on Sunday with his family. He ate many different foods but was the only one in the family to eat the undercooked hot dogs served by the hosts. Monday morning, he woke up feeling achy and nauseous, and he was running a fever of 38 °C (100.4 °F). His parents, assuming Michael had caught the flu, made him stay home from school and limited his activities. But after 4 days, Michael began to experience severe headaches, and his fever spiked to 40 °C (104 °F). Growing worried, his parents finally decide to take Michael to a nearby clinic.

  • What signs and symptoms is Michael experiencing?
  • What do these signs and symptoms tell us about the stage of Michael’s disease?

Jump to the next Clinical Focus box.

A disease is any condition in which the normal structure or functions of the body are damaged or impaired. Physical injuries or disabilities are not classified as disease, but there can be several causes for disease, including infection by a pathogen, genetics (as in many cancers or deficiencies), noninfectious environmental causes, or inappropriate immune responses. Our focus in this chapter will be on infectious diseases, although when diagnosing infectious diseases, it is always important to consider possible noninfectious causes.

Signs and Symptoms of Disease

An infection is the successful colonization of a host by a microorganism. Infections can lead to disease, which causes signs and symptoms resulting in a deviation from the normal structure or functioning of the host. Microorganisms that can cause disease are known as pathogens.

The sign s of disease are objective and measurable, and can be directly observed by a clinician. Vital signs, which are used to measure the body’s basic functions, include body temperature (normally 37 °C [98.6 °F]), heart rate (normally 60–100 beats per minute), breathing rate (normally 12–18 breaths per minute), and blood pressure (normally between 90/60 and 120/80 mm Hg). Changes in any of the body’s vital signs may be indicative of disease. For example, having a fever (a body temperature significantly higher than 37 °C or 98.6 °F) is a sign of disease because it can be measured.

In addition to changes in vital signs, other observable conditions may be considered signs of disease. For example, the presence of antibodies in a patient’s serum (the liquid portion of blood that lacks clotting factors) can be observed and measured through blood tests and, therefore, can be considered a sign. However, it is important to note that the presence of antibodies is not always a sign of an active disease. Antibodies can remain in the body long after an infection has resolved also, they may develop in response to a pathogen that is in the body but not currently causing disease.

Unlike signs, symptom s of disease are subjective. Symptoms are felt or experienced by the patient, but they cannot be clinically confirmed or objectively measured. Examples of symptoms include nausea, loss of appetite, and pain. Such symptoms are important to consider when diagnosing disease, but they are subject to memory bias and are difficult to measure precisely. Some clinicians attempt to quantify symptoms by asking patients to assign a numerical value to their symptoms. For example, the Wong-Baker Faces pain-rating scale asks patients to rate their pain on a scale of 0–10. An alternative method of quantifying pain is measuring skin conductance fluctuations. These fluctuations reflect sweating due to skin sympathetic nerve activity resulting from the stressor of pain. 1

A specific group of signs and symptoms characteristic of a particular disease is called a syndrome . Many syndromes are named using a nomenclature based on signs and symptoms or the location of the disease. Table 15.1 lists some of the prefixes and suffixes commonly used in naming syndromes.

Nomenclature of Symptoms
Affix Meaning Example
cyto- cell cytopenia: reduction in the number of blood cells
hepat- of the liver hepatitis: inflammation of the liver
-pathy disease neuropathy: a disease affecting nerves
-emia of the blood bacteremia: presence of bacteria in blood
-itis inflammation colitis: inflammation of the colon
-lysis destruction hemolysis: destruction of red blood cells
-oma tumor lymphoma: cancer of the lymphatic system
-osis diseased or abnormal condition leukocytosis: abnormally high number of white blood cells
-derma of the skin keratoderma: a thickening of the skin

Clinicians must rely on signs and on asking questions about symptoms, medical history, and the patient’s recent activities to identify a particular disease and the potential causative agent. Diagnosis is complicated by the fact that different microorganisms can cause similar signs and symptoms in a patient. For example, an individual presenting with symptoms of diarrhea may have been infected by one of a wide variety of pathogenic microorganisms. Bacterial pathogens associated with diarrheal disease include Vibrio cholerae , Listeria monocytogenes , Campylobacter jejuni , and enteropathogenic Escherichia coli ( EPEC ). Viral pathogens associated with diarrheal disease include norovirus and rotavirus. Parasitic pathogens associated with diarrhea include Giardia lamblia and Cryptosporidium parvum . Likewise, fever is indicative of many types of infection, from the common cold to the deadly Ebola hemorrhagic fever .

Finally, some diseases may be asymptomatic or subclinical , meaning they do not present any noticeable signs or symptoms. For example, most individual infected with herpes simplex virus remain asymptomatic and are unaware that they have been infected.

Check Your Understanding

Classifications of Disease

The World Health Organization’s (WHO) International Classification of Diseases (ICD) is used in clinical fields to classify diseases and monitor morbidity (the number of cases of a disease) and mortality (the number of deaths due to a disease). In this section, we will introduce terminology used by the ICD (and in health-care professions in general) to describe and categorize various types of disease.

An infectious disease is any disease caused by the direct effect of a pathogen. A pathogen may be cellular (bacteria, parasites, and fungi) or acellular (viruses, viroids, and prions). Some infectious diseases are also communicable , meaning they are capable of being spread from person to person through either direct or indirect mechanisms. Some infectious communicable diseases are also considered contagious diseases, meaning they are easily spread from person to person. Not all contagious diseases are equally so the degree to which a disease is contagious usually depends on how the pathogen is transmitted. For example, measles is a highly contagious viral disease that can be transmitted when an infected person coughs or sneezes and an uninfected person breathes in droplets containing the virus. Gonorrhea is not as contagious as measles because transmission of the pathogen ( Neisseria gonorrhoeae ) requires close intimate contact (usually sexual) between an infected person and an uninfected person.

Diseases that are contracted as the result of a medical procedure are known as iatrogenic disease s. Iatrogenic diseases can occur after procedures involving wound treatments, catheterization, or surgery if the wound or surgical site becomes contaminated. For example, an individual treated for a skin wound might acquire necrotizing fasciitis (an aggressive, “flesh-eating” disease) if bandages or other dressings became contaminated by Clostridium perfringens or one of several other bacteria that can cause this condition.

Diseases acquired in hospital settings are known as nosocomial disease s. Several factors contribute to the prevalence and severity of nosocomial diseases. First, sick patients bring numerous pathogens into hospitals, and some of these pathogens can be transmitted easily via improperly sterilized medical equipment, bed sheets, call buttons, door handles, or by clinicians, nurses, or therapists who do not wash their hands before touching a patient. Second, many hospital patients have weakened immune systems, making them more susceptible to infections. Compounding this, the prevalence of antibiotics in hospital settings can select for drug-resistant bacteria that can cause very serious infections that are difficult to treat.

Certain infectious diseases are not transmitted between humans directly but can be transmitted from animals to humans. Such a disease is called zoonotic disease (or zoonosis ). According to WHO, a zoonosis is a disease that occurs when a pathogen is transferred from a vertebrate animal to a human however, sometimes the term is defined more broadly to include diseases transmitted by all animals (including invertebrates). For example, rabies is a viral zoonotic disease spread from animals to humans through bites and contact with infected saliva. Many other zoonotic diseases rely on insects or other arthropods for transmission. Examples include yellow fever (transmitted through the bite of mosquitoes infected with yellow fever virus) and Rocky Mountain spotted fever (transmitted through the bite of ticks infected with Rickettsia rickettsii ).

In contrast to communicable infectious diseases, a noncommunicable infectious disease is not spread from one person to another. One example is tetanus , caused by Clostridium tetani , a bacterium that produces endospores that can survive in the soil for many years. This disease is typically only transmitted through contact with a skin wound it cannot be passed from an infected person to another person. Similarly, Legionnaires disease is caused by Legionella pneumophila , a bacterium that lives within amoebae in moist locations like water-cooling towers. An individual may contract Legionnaires disease via contact with the contaminated water, but once infected, the individual cannot pass the pathogen to other individuals.

In addition to the wide variety of noncommunicable infectious diseases, noninfectious disease s (those not caused by pathogens) are an important cause of morbidity and mortality worldwide. Noninfectious diseases can be caused by a wide variety factors, including genetics, the environment, or immune system dysfunction, to name a few. For example, sickle cell anemia is an inherited disease caused by a genetic mutation that can be passed from parent to offspring (Figure 15.2). Other types of noninfectious diseases are listed in Table 15.2.

Types of Noninfectious Diseases
Type Definition Example
Inherited A genetic disease Sickle cell anemia
Congenital Disease that is present at or before birth Down syndrome
Degenerative Progressive, irreversible loss of function Parkinson disease (affecting central nervous system)
Nutritional deficiency Impaired body function due to lack of nutrients Scurvy (vitamin C deficiency)
Endocrine Disease involving malfunction of glands that release hormones to regulate body functions Hypothyroidism – thyroid does not produce enough thyroid hormone, which is important for metabolism
Neoplastic Abnormal growth (benign or malignant) Some forms of cancer
Idiopathic Disease for which the cause is unknown Idiopathic juxtafoveal retinal telangiectasia (dilated, twisted blood vessels in the retina of the eye)

Link to Learning

Check Your Understanding

  • Describe how a disease can be infectious but not contagious.
  • Explain the difference between iatrogenic disease and nosocomial disease.

Periods of Disease

The five periods of disease (sometimes referred to as stages or phases) include the incubation, prodromal, illness, decline, and convalescence periods (Figure 15.3). The incubation period occurs in an acute disease after the initial entry of the pathogen into the host (patient). It is during this time the pathogen begins multiplying in the host. However, there are insufficient numbers of pathogen particles (cells or viruses) present to cause signs and symptoms of disease. Incubation periods can vary from a day or two in acute disease to months or years in chronic disease, depending upon the pathogen. Factors involved in determining the length of the incubation period are diverse, and can include strength of the pathogen, strength of the host immune defenses, site of infection, type of infection, and the size infectious dose received. During this incubation period, the patient is unaware that a disease is beginning to develop.

The prodromal period occurs after the incubation period. During this phase, the pathogen continues to multiply and the host begins to experience general signs and symptoms of illness, which typically result from activation of the immune system, such as fever, pain, soreness, swelling, or inflammation. Usually, such signs and symptoms are too general to indicate a particular disease. Following the prodromal period is the period of illness , during which the signs and symptoms of disease are most obvious and severe.

The period of illness is followed by the period of decline , during which the number of pathogen particles begins to decrease, and the signs and symptoms of illness begin to decline. However, during the decline period, patients may become susceptible to developing secondary infections because their immune systems have been weakened by the primary infection. The final period is known as the period of convalescence . During this stage, the patient generally returns to normal functions, although some diseases may inflict permanent damage that the body cannot fully repair.

Infectious diseases can be contagious during all five of the periods of disease. Which periods of disease are more likely to associated with transmissibility of an infection depends upon the disease, the pathogen, and the mechanisms by which the disease develops and progresses. For example, with meningitis (infection of the lining of brain), the periods of infectivity depend on the type of pathogen causing the infection. Patients with bacterial meningitis are contagious during the incubation period for up to a week before the onset of the prodromal period, whereas patients with viral meningitis become contagious when the first signs and symptoms of the prodromal period appear. With many viral diseases associated with rashes (e.g., chickenpox , measles , rubella , roseola ), patients are contagious during the incubation period up to a week before the rash develops. In contrast, with many respiratory infections (e.g., colds, influenza , diphtheria , strep throat , and pertussis ) the patient becomes contagious with the onset of the prodromal period. Depending upon the pathogen, the disease, and the individual infected, transmission can still occur during the periods of decline, convalescence, and even long after signs and symptoms of the disease disappear. For example, an individual recovering from a diarrheal disease may continue to carry and shed the pathogen in feces for some time, posing a risk of transmission to others through direct contact or indirect contact (e.g., through contaminated objects or food).

Check Your Understanding

  • Name some of the factors that can affect the length of the incubation period of a particular disease.

Acute and Chronic Diseases

The duration of the period of illness can vary greatly, depending on the pathogen, effectiveness of the immune response in the host, and any medical treatment received. For an acute disease , pathologic changes occur over a relatively short time (e.g., hours, days, or a few weeks) and involve a rapid onset of disease conditions. For example, influenza (caused by Influenzavirus) is considered an acute disease because the incubation period is approximately 1–2 days. Infected individuals can spread influenza to others for approximately 5 days after becoming ill. After approximately 1 week, individuals enter the period of decline.

For a chronic disease , pathologic changes can occur over longer time spans (e.g., months, years, or a lifetime). For example, chronic gastritis (inflammation of the lining of the stomach) is caused by the gram-negative bacterium Helicobacter pylori . H. pylori is able to colonize the stomach and persist in its highly acidic environment by producing the enzyme urease, which modifies the local acidity, allowing the bacteria to survive indefinitely. 2 Consequently, H. pylori infections can recur indefinitely unless the infection is cleared using antibiotics. 3 Hepatitis B virus can cause a chronic infection in some patients who do not eliminate the virus after the acute illness. A chronic infection with hepatitis B virus is characterized by the continued production of infectious virus for 6 months or longer after the acute infection, as measured by the presence of viral antigen in blood samples.

In latent disease s, as opposed to chronic infections, the causal pathogen goes dormant for extended periods of time with no active replication. Examples of diseases that go into a latent state after the acute infection include herpes (herpes simplex viruses [HSV-1 and HSV-2]), chickenpox ( varicella-zoster virus [VZV]), and mononucleosis ( Epstein-Barr virus [EBV]). HSV-1, HSV-2, and VZV evade the host immune system by residing in a latent form within cells of the nervous system for long periods of time, but they can reactivate to become active infections during times of stress and immunosuppression. For example, an initial infection by VZV may result in a case of childhood chickenpox, followed by a long period of latency. The virus may reactivate decades later, causing episodes of shingles in adulthood. EBV goes into latency in B cells of the immune system and possibly epithelial cells it can reactivate years later to produce B-cell lymphoma.


Stages of Pathogenesis

To cause disease, a pathogen must successfully achieve four steps or stages of pathogenesis : exposure (contact), adhesion (colonization), invasion, and infection. The pathogen must be able to gain entry to the host, travel to the location where it can establish an infection, evade or overcome the host’s immune response, and cause damage (i.e., disease) to the host. In many cases, the cycle is completed when the pathogen exits the host and is transmitted to a new host.


Life Cycle of Viruses with Animal Hosts

Lytic animal viruses follow similar infection stages to bacteriophages: attachment, penetration, biosynthesis, maturation, and release (Figure 6.10). However, the mechanisms of penetration, nucleic-acid biosynthesis, and release differ between bacterial and animal viruses. After binding to host receptors, animal viruses enter through endocytosis (engulfment by the host cell) or through membrane fusion (viral envelope with the host cell membrane). Many viruses are host specific, meaning they only infect a certain type of host and most viruses only infect certain types of cells within tissues. This specificity is called a tissue tropism. Examples of this are demonstrated by the poliovirus , which exhibits tropism for the tissues of the brain and spinal cord, or the influenza virus , which has a primary tropism for the respiratory tract.

Figure 6.10. In influenza virus infection, viral glycoproteins attach the virus to a host epithelial cell. As a result, the virus is engulfed. Viral RNA and viral proteins are made and assembled into new virions that are released by budding.

Animal viruses do not always express their genes using the normal flow of genetic information—from DNA to RNA to protein. Some viruses have a dsDNA genome like cellular organisms and can follow the normal flow. However, others may have ssDNA , dsRNA , or ssRNA genomes. The nature of the genome determines how the genome is replicated and expressed as viral proteins. If a genome is ssDNA, host enzymes will be used to synthesize a second strand that is complementary to the genome strand, thus producing dsDNA. The dsDNA can now be replicated, transcribed, and translated similar to host DNA.

If the viral genome is RNA, a different mechanism must be used. There are three types of RNA genome: dsRNA, positive (+) single-strand (+ssRNA) or negative (−) single-strand RNA (−ssRNA). If a virus has a +ssRNA genome, it can be translated directly to make viral proteins. Viral genomic +ssRNA acts like cellular mRNA. However, if a virus contains a −ssRNA genome, the host ribosomes cannot translate it until the −ssRNA is replicated into +ssRNA by viral RNA-dependent RNA polymerase (RdRP) (Figure 6.11). The RdRP is brought in by the virus and can be used to make +ssRNA from the original −ssRNA genome. The RdRP is also an important enzyme for the replication of dsRNA viruses, because it uses the negative strand of the double-stranded genome as a template to create +ssRNA. The newly synthesized +ssRNA copies can then be translated by cellular ribosomes.

Figure 6.11. RNA viruses can contain +ssRNA that can be directly read by the ribosomes to synthesize viral proteins. Viruses containing −ssRNA must first use the −ssRNA as a template for the synthesis of +ssRNA before viral proteins can be synthesized.

An alternative mechanism for viral nucleic acid synthesis is observed in the retroviruses, which are +ssRNA viruses (Figure 6.12). Single-stranded RNA viruses such as HIV carry a special enzyme called reverse transcriptase within the capsid that synthesizes a complementary ssDNA (cDNA) copy using the +ssRNA genome as a template. The ssDNA is then made into dsDNA, which can integrate into the host chromosome and become a permanent part of the host. The integrated viral genome is called a provirus. The virus now can remain in the host for a long time to establish a chronic infection. The provirus stage is similar to the prophage stage in a bacterial infection during the lysogenic cycle. However, unlike prophage, the provirus does not undergo excision after splicing into the genome.

Figure 6.12. HIV, an enveloped, icosahedral retrovirus, attaches to a cell surface receptor of an immune cell and fuses with the cell membrane. Viral contents are released into the cell, where viral enzymes convert the single-stranded RNA genome into DNA and incorporate it into the host genome. (credit: modification of work by NIAID, NIH)


Acknowledgements

The authors would like to thank Prof. Jean-Pierre Perreault, Department of Biochemistry, Université de Sherbrooke, Canada for fruitful discussions during the manuscript’s preparation. This work was supported in part by Japan Society for the Promotion of Science KAKENHI grant no. 24380026 and 15H04455. CRA received Japan Society for the Promotion of Science Postdoctoral Fellowship for Overseas Researchers. The funders of this work had no role in study design, data collection and analysis, nor in the decision to publish or in the preparation of the manuscript.


Supporting information

S1 Fig. Effects of HCV-downregulated circRNAs and further control circRNAs on HCV RNA abundances.

Effects of control and three siRNAs directed against circRMB39 (A,B) or circPMS1 RNA (C,D) on HCV RNA abundance. RNA abundance was determined by RT-qPCR. (E) Effects of various circRNA depletions on HCV RNA abundances, examined by Northern blot analyses.

S2 Fig. Resistance of circPSD3 and circPTP4A2 to RNase R.

Total RNA from JFH1-infected cells was treated with or without RNase R. RNA abundances were analyzed using RT-qPCR. The RNA abundances are compared to RNA abundances from the untreated samples (set to 1.0). circPTP4A2 is derived from protein tyrosine phosphatase 4A2 mRNA.

S3 Fig. Cell viability of circPSD3 RNA-depleted cells.

The cell viability of control siRNA and four circPSD3 siRNAs were measured at two days after infection. The data are representative of three independent experiments.

S4 Fig. Effects of circPSD3 depletion on extracellular HCV JFH1 virus production.

Huh7 cells were transfected with non-targeting control siRNAs (siCtrl) or siRNA targeting circPSD3 (si-circPSD3). At one day post transfection, cells were infected with JFH-1 virus at 0.1 moi or 1 moi. Supernatants were collected at three days post infection and viral titers were determined by focus forming assays (FFU).

S5 Fig. Effects of HCV infection and circPSD3 depletion on eIF4A3 protein and RNA abundances.

(A) eIF4A3 protein abundances were measured by Western blot at three days after HCV JFH-1 infection. Three independent experiments are shown. (B) eIF4A3 mRNA abundances in siRNA-transfected cells that were further infected with HCV. Mock cells are non-transfected and non-infected cells. Data from RT-qPCR reactions are shown. (C) Effects of circPSD3 depletion on eIF4A3 mRNA abundances in uninfected cells. Data from RT-PCR are shown.

S6 Fig. Effects of eIF4A3 abundances on NMD and HCV infection.

(A) Cells were transfected with siRNA targeting circPSD3 or eIF4A3, or co-transfected with both siRNAs. At one day post transfection, cells were infected with JFH-1 at 0.5 moi. ASNS abundances were measured 3 days post infection by RT-qPCR. (B) Cells were transfected with plasmid peIF4A3. At one day post transfection, cells were infected with JFH-1 at 0.5 moi and incubated for 3 days. HCV RNA abundances were measured by RT-PCR. (C) Knockdown efficiencies of individual siRNA transfections on circPSD3 and linear PSD3 RNA abundances. (D) eIF4A3 RNA abundances after transfection with siRNA or peIF4A3 plasmid. RNA abundances were evaluated by RT-qPCR after cells were transfected and further infected for 3 days. Data from three independent experiments are shown (* p<0.05 ****p<0.0001).

S1 Table. List of selected circRNAs.

The table shows the circRNAs used in this study, including gene name, circle name, sizes of circRNAs, linear RNAs, and primers (5’-3’) used for the qPCR-based validations.


References

Ag࿎ro, J., Gómez-Aix, C., Sempere, R. N., Garc໚-Villalba, J., Garc໚-Nú༞z, J., Hernando, Y., et al. (2018). Stable and broad spectrum cross-protection against pepino mosaic virus attained by mixed infection. Front. Plant Sci. 9:1810. doi: 10.3389/fpls.2018.01810

Aiewsakun, P., and Katzourakis, A. (2015). Endogenous viruses: connecting recent and ancient viral evolution. Virology 479-480, 26�. doi: 10.1016/j.virol.2015.02.011

Alexander, H. M., Bruns, E., Schebor, H., and Malmstrom, C. M. (2017). Crop-associated virus infection in a native perennial grass: reduction in plant fitness and dynamic patterns of virus detection. J. Ecol. 105, 1021�. doi: 10.1111/1365-2745.12723

Ashby, M. K., Warry, A., Bejarano, E. R., Khashoggi, A., Burrell, M., and Lichtenstein, C. P. (1997). Analysis of multiple copies of geminiviral DNA in the genome of four closely related Nicotiana species suggest a unique integration event. Plant Mol. Biol. 35, 313�.

Aus dem Siepen, M., Pohl, J. O., Koo, B. J., Wege, C., and Jeske, H. (2005). Poinsettia latent virus is not a cryptic virus, but a natural polerovirus-sobemovirus hybrid. Virology 336, 240�. doi: 10.1016/j.virol.2005.03.020

Barba, M., Czosnek, H., and Hadidi, A. (2014). Historical perspective, development and applications of next-generation sequencing in plant virology. Viruses 6, 106�. doi: 10.3390/v6010106

Barton, E. S., White, D. W., Cathelyn, J. S., Brett-McClellan, K. A., Engle, M., Diamond, M. S., et al. (2007). Herpesvirus latency confers symbiotic protection from bacterial infection. Nature 447, 326�. doi: 10.1038/nature05762

Bejarano, E. R., Khashoggi, A., Witty, M., and Lichtenstein, C. (1996). Integration of multiple repeats of geminiviral DNA into the nuclear genome of tobacco during evolution. Proc. Natl. Acad. Sci. U.S.A. 93, 759�. doi: 10.1073/pnas.93.2.759

Bem, F., and Murant, A. F. (1979). Host range, purification and serological properties of heracleum latent virus. Ann. Appl. Biol. 92, 243�. doi: 10.1111/j.1744-7348.1979.tb03870.x

Bernardo, P., Golden, M., Akram, M., Naimuddin Nadarajan, N., Fernandez, E., Granier, M., et al. (2013). Identification and characterization of a highly divergent geminivirus: evolutionary and taxonomic implications. Virus Res. 177, 35�. doi: 10.1016/j.virusres.2013.07.006

Bernardo, P., Muhire, B., Francois, S., Deshoux, M., Hartnady, P., Farkas, K., et al. (2016). Molecular characterization and prevalence of two capulaviruses: Alfalfa leaf curl virus from France and Euphorbia caput-medusae latent virus from South Africa. Virology 493, 142�. doi: 10.1016/j.virol.2016.03.016

Bertsch, C., Beuve, M., Dolja, V. V., Wirth, M., Pelsy, F., Herrbach, E., et al. (2009). Retention of the virus-derived sequences in the nuclear genome of grapevine as a potential pathway to virus resistance. Biol. Direct 4:21. doi: 10.1186/1745-6150-4-21

Boccardo, G., Lisa, V., Luisoni, E., and Milne, R. G. (1987). Cryptic plant viruses. Adv. Virus Res. 32, 171�. doi: 10.1016/s0065-3527(08)60477-7

Boccardo, G., Milne, R. G., Luisoni, E., Lisa, V., and Accotto, G. P. (1985). Three seedborne cryptic viruses containing double-stranded RNA isolated from white clover. Virology 147, 29�. doi: 10.1016/0042-6822(85)90224-7

Bos, L., Huttinga, H., and Maat, D. Z. (1980). Spinach latent virus, a new ilarvirus seed-borne in Spinacia oleracea. Netherlands J. Plant Pathol. 86, 79�. doi: 10.1007/bf01974337

Bousalem, M., Douzery, E. J. P., and Seal, S. E. (2008). Taxonomy, molecular phylogeny and evolution of plant reverse transcribing viruses (family Caulimoviridae) inferred from full-length genome and reverse transcriptase sequences. Arch. Virol. 153, 1085�. doi: 10.1007/s00705-008-0095-9

Boyd, E. F. (2012). Bacteriophage-encoded bacterial virulence factors and phage-pathogenicity island interactions. Adv. Virus Res. 82, 91�. doi: 10.1016/B978-0-12-394621-8.00014-5

Brüssow, H., Canchaya, C., and Hardt, W. D. (2004). Phages and the evolution of bacterial pathogens: from genomic rearrangements to lysogenic conversion. Microbiol. Mol. Biol. Rev. 68, 560�. doi: 10.1128/MMBR.68.3.560-602.2004

Bueso, E., Serrano, R., Pallás, V., and Sánchez-Navarro, J. A. (2017). Seed tolerance to deterioration in arabidopsis is affected by virus infection. Plant Physiol. Biochem. 116, 1𠄸. doi: 10.1016/j.plaphy.2017.04.020

Chabannes, M., and Iskra-Caruana, M. L. (2013). Endogenous pararetroviruses - a reservoir of virus infection in plants. Curr. Opin. Virol. 3, 615�. doi: 10.1016/j.coviro.2013.08.012

Chen, S., and Kishima, Y. (2016). Endogenous pararetroviruses in rice genomes as a fossil record useful for the emerging field of palaeovirology. Mol. Plant Pathol. 17, 1317�. doi: 10.1111/mpp.12490

Chen, S., Liu, R., Koyanagi, K. O., and Kishima, Y. (2014). Rice genomes recorded ancient pararetrovirus activities: virus genealogy and multiple origins of endogenization during rice speciation. Virology 471, 141�. doi: 10.1016/j.virol.2014.09.014

Chiba, S., Kondo, H., Tani, A., Saisho, D., Sakamoto, W., Kanematsu, S., et al. (2011). Widespread endogenization of genome sequences of non-retroviral RNA viruses into plant genomes. PLoS Pathog. 7:e1002146. doi: 10.1371/journal.ppat.1002146

Chu, H., Jo, Y., and Cho, W. K. (2014). Evolution of endogenous non-retroviral genes integrated into plant genomes. Curr. Plant Biol. 1, 55�. doi: 10.1016/j.cpb.2014.07.002

Diop, S. I., Geering, A. D. W., Alfama-Depauw, F., Loaec, M., Teycheney, P. Y., and Maumus, F. (2018). Tracheophyte genomes keep track of the deep evolution of the Caulimoviridae. Sci. Rep. 8:572. doi: 10.1038/s41598-017-16399-x

Edson, K. M., Vinson, S. B., Stoltz, D. B., and Summers, M. D. (1981). Virus in a parasitoid wasp: suppression of the cellular immune response in the parasitoid’s host. Science 211, 582�. doi: 10.1126/science.7455695

Eid, S., and Pappu, H. R. (2014). Expression of endogenous para-retroviral genes and molecular analysis of the integration events in its plant host Dahlia variabilis. Virus Genes 48, 153�. doi: 10.1007/s11262-013-0998-8

Félix, M. R., Joana, M. S., Cardoso, J. M. S., Oliveira, S., and Clara, M. I. E. (2007). Biological and molecular characterization of Olive latent virus 1. Plant Viruses 1, 170�.

Feschotte, C., and Gilbert, C. (2012). Endogenous viruses: insights into viral evolution and impact on host biology. Nat. Rev. Genet. 13, 283�. doi: 10.1038/nrg3199

Fraile, A., McLeish, M. J., Pagán, I., González-Jara, P., Pi༞ro, D., and Garc໚-Arenal, F. (2017). Environmental heterogeneity and the evolution of plant-virus interactions: viruses in wild pepper populations. Virus Res. 241, 68�. doi: 10.1016/j.virusres.2017.05.015

Fukuhara, T. (2019). Endornaviruses: persistent dsRNA viruses with symbiotic properties in diverse eukaryotes. Virus Genes 55, 165�. doi: 10.1007/s11262-019-01635-5

Fukuhara, T., Tabara, M., Koiwa, H., and Takahashi, H. (2019). Effect on tomato plants of asymptomatic infection with southern tomato virus. Arch. Virol. doi: 10.1007/s00705-019-04436-1 [Epub ahead of print].

Gallitelli, D., Martelli, G. P., and Di Franco, A. (1989). Grapevine Algerian latent virus, a newly recognized Tombusvirus. Phytoparasitica 17, 61�.

Gallitelli, D., and Savino, V. (1985). Olive latent virus 1, an isometric virus with a single RNA species isolated from olive in Apulia, Southern Italy. Ann. Appl. Biol. 106, 295�. doi: 10.1111/j.1744-7348.1985.tb03119.x

Geering, A. D. W., Maumus, F., Copetti, D., Choisne, N., Zwickl, D. J., Zytnicki, M., et al. (2014). Endogenous florendoviruses are major components of plant genomes and hallmarks of virus evolution. Nat. Commun. 5:5269. doi: 10.1038/ncomms6269

Geering, A. D. W., Scharaschkin, T., and Teycheney, P.-Y. (2010). The classification and nomenclature of endogenous viruses of the family Caulimoviridae. Arch. Virol. 155, 123�. doi: 10.1007/s00705-009-0488-4

Goic, B., Stapleford, K. A., Frangeul, L., Doucet, A. J., Gausson, V., Blanc, H., et al. (2016). Virus-derived DNA drives mosquito vector tolerance to arboviral infection. Nat. Commun. 7:12410. doi: 10.1038/ncomms12410

Goic, B., Vodovar, N., Mondotte, J. A., Monot, C., Frangeul, L., Blanc, H., et al. (2013). RNA-mediated interference and reverse transcription control the persistence of RNA viruses in the insect model Drosophila. Nat. Immunol. 14, 396�. doi: 10.1038/ni.2542

Grimová, L., and Ryšánek, P. (2012). Apricot latent virus - review. Hort. Sci. 39, 144�. doi: 10.17221/260/2011-hortsci

Groen, S. C., Jiang, S., Murphy, A. M., Cunniffe, N. J., Westwood, J. H., Davey, M. P., et al. (2016). Virus infection of plants alters pollinator preference: a payback for susceptible hosts? PLoS Pathog. 12:e1005790. doi: 10.1371/journal.ppat.1005906

Guy, P. L., and Sward, R. J. (1991). Ryegrass mosaic and ryegrass cryptic virus in Australia. Acta Phytopathol. Ent. Hungarica 26, 199�.

Harper, G., Hull, R., Lockhart, B., and Olszewski, N. (2002). Viral sequences integrated into plant genomes. Annu. Rev. Phytopathol. 40, 119�. doi: 10.1146/annurev.phyto.40.120301.105642

Harper, G., Osuji, J. O., Heslop-Harrison, J. S., and Hull, R. (1999). Integration of banana streak badnavirus into the Musa genome: molecular and cytogenetic evidence. Virology 255, 207�. doi: 10.1006/viro.1998.9581

Harth, J. E., Ferrari, M. J., Helms, A. M., Tooker, J. F., and Stephenson, A. G. (2018). Zucchini yellow mosaic virus infection limits establishment and severity of powdery mildew in wild populations of Cucurbita pepo. Front. Plant Sci. 9:792. doi: 10.3389/fpls.2018.01815

Herschlag, R., Escalante, C., de Souto, E. R., Khankhum, S., Okada, R., and Valverde, R. A. (2019). Occurrence of putative endornaviruses in non-cultivated plant species in South Louisiana. Arch. Virol. 164, 1863�. doi: 10.1007/s00705-019-04270-5

Hohn, T., Richert-Poeggeler, K. R., Staginnus, C., Harper, G., Schwarzacher, T., Teo, C. H., et al. (2008). 𠇎volution of integrated plant viruses,” in Plant Virus Evolution, ed. M. J. Roossinck (Berlin: Springer), 53�. doi: 10.1007/978-3-540-75763-4_4

Holmes, E. C. (2011). The evolution of endogenous viral elements. Cell Host Microbe 10, 368�. doi: 10.1016/j.chom.2011.09.002

Hull, R. (2014). Plant Virology, 5th Edn. Cambridge, MA: Academic Press. doi: 10.1016/C2010-0-64974-1

Huth, W., Lesemann, D. E., Götz, R., and Vetten, H. J. (1995). Some properties of Lolium latent virus. Agronomie 15:508. doi: 10.1094/PD-90-0528C

Iskra-Caruana, M. L., Baurens, F. C., Gayral, P., and Chabannes, M. (2010). A four-partner plant-virus interaction: enemies can also come from within. Mol. Plant Microbe Interact. 23, 1394�. doi: 10.1094/MPMI-05-10-0107

Jakowitsch, J., Mette, M. F., van der Winden, J., Matske, M. A., and Matske, A. J. M. (1999). Integrated pararetroviral sequences define a unique class of dispersed repetitive DNA in plants. Proc. Nat. Acad. Sci. U.S.A. 96, 13241�. doi: 10.1073/pnas.96.23.13241

Kamitani, M., Nagano, A. J., Honjo, M. N., and Kudoh, H. (2016). RNA-Seq reveals virus–virus and virus–plant interactions in nature. FEMS Microbiol. Ecol. 92:fiw176. doi: 10.1093/femsec/fiw176

Khankhum, S., and Valverde, R. A. (2018). Physiological traits of endornavirus-infected and endornavirus-free common bean (Phaseolus vulgaris) cv Black Turtle Soup. Arch. Virol. 163, 1051�. doi: 10.1007/s00705-018-3702-4

Koganezawa, H., Yanase, H., Ochiai, M., and Sakuma, T. (1985). Anisometric virus-like particle isolated from russet ring-diseased apple. Ann. Phytopathol. Soc. Japan 51:363.

Kostin, V. D., and Volkov, Y. G. (1976). Some properties of the virus affecting Plantago asiatica L. Virusnye Bolezni Rastenij Dalnego Vostoka 25, 205�.

Kreuze, J. F., Perez, A., Untiveros, M., Quispe, D., Fuentes, S., Barker, I., et al. (2009). Complete viral genome sequence and discovery of novel viruses by deep sequencing of small RNAs: a generic method for diagnosis, discovery and sequencing of viruses. Virology 388, 1𠄷. doi: 10.1016/j.virol.2009.03.024

Kunii, M., Kanda, M., Nagano, H., Uyeda, I., Kishima, Y., and Sano, Y. (2004). Reconstruction of putative DNA virus from endogenous rice tungro bacilliform virus-like sequences in the rice genome: implications for integration and evolution. BMC Genomics 5:80. doi: 10.1186/1471-2164-5-80

Li, C., Yoshikawa, N., Takahashi, T., Ito, T., Yoshida, K., and Koganezawa, H. (2000). Nucleotide sequence and genome organization of apple latent spherical virus: a new virus classified into the family Comoviridae. J. Gen. Virol. 81, 541�. doi: 10.1099/0022-1317-81-2-541

Lister, R. M. (1964). Strawberry latent ringspot: a new nematode-bome virus. Ann. Appl. Biol. 54, 167�. doi: 10.1111/j.1744-7348.1964.tb01180.x

Little, T. J., Shuker, D. M., Colegrave, N., Day, T., and Graham, A. L. (2010). The coevolution of virulence: tolerance in perspective. PLoS Pathog. 6:e1001006. doi: 10.1371/journal.ppat.1001006

Liu, H., Fu, Y., Jiang, D., Li, G., Xie, J., Cheng, J., et al. (2010). Widespread horizontal gene transfer from double-stranded RNA viruses to eukaryotic nuclear genomes. J. Virol. 84, 11879�. doi: 10.1128/JVI.00955-10

Liu, H., Fu, Y., Li, B., Yu, X., Xie, J., Cheng, J., et al. (2011). Widespread horizontal gene transfer from circular single-stranded DNA viruses to eukaryotic genomes. BMC Evol. Biol. 11:276. doi: 10.1186/1471-2148-11-276

Liu, H., Fu, Y., Xie, J., Cheng, J., Ghabrial, S. A., Li, G., et al. (2012). Discovery of novel dsRNA viral sequences by in silico cloning and implications for viral diversity, host range and evolution. PLoS One 7:e42147. doi: 10.1371/journal.pone.0042147

Lockhart, B. E., Menke, J., Dahal, G., and Olszewski, N. E. (2000). Characterization and genomic analysis of Tobacco vein clearing virus, a plant pararetrovirus that is transmitted vertically and related to sequences integrated in the host genome. J. Gen. Virol. 81, 1579�. doi: 10.1099/0022-1317-81-6-1579

Lovato, A., Faoro, F., Gambino, G., Maffi, D., Bracale, M., Polverari, A., et al. (2014). Construction of a synthetic infectious cDNA clone of Grapevine algerian latent virus (GALV-Nf) and its biological activity in Nicotiana benthamiana and grapevine plants. Virol. J. 11:186. doi: 10.1186/1743-422X-11-186

Malmstrom, C. M., and Alexander, H. M. (2016). Effects of crop viruses on wild plants. Curr. Opin. Virol. 19, 30�. doi: 10.1016/j.coviro.2016.06.008

Maroon-Lango, C., Hammond, J., Warnke, S., Li, R., and Mock, R. (2006). First report of Lolium latent virus in ryegrass in the USA. Plant Dis. 90:528. doi: 10.1094/PD-90-0528C

Márquez, L. M., Redman, R. S., Rodriguez, R. J., and Roossinck, M. J. (2007). A virus in a fungus in a plant: three-way symbiosis required for thermal tolerance. Science 315, 513�. doi: 10.1126/science.1136237

Martelli, G. P., and Jelkmann, W. (1998). Foveavirus, a new plant virus genus. Arch. Virol. 143, 1245�. doi: 10.1007/s007050050372

Martin, R. R., Zhou, J., and Tzanetakis, I. E. (2011). Blueberry latent virus: an amalgam of the Partitiviridae and Totiviridae. Virus Res. 155, 175�. doi: 10.1016/j.virusres.2010.09.020

Matzke, M., Gregor, W., Mette, M. F., Aufsatz, W., Kanno, T., Jakowitsch, J., et al. (2004). Endogenous pararetroviruses of allotetraploid Nicotiana tabacum and its diploid progenitors, N. sylvestris and N. tomentosiformis. Biol. J. Lin. Soc. 82, 627�. doi: 10.1111/j.1095-8312.2004.00347.x

Mauck, K. E., De Moraes, C. M., and Mescher, M. C. (2010). Deceptive chemical signals induced by a plant virus attract insect vectors to inferior hosts. Proc. Natl. Acad. Sci. U.S.A. 107, 3600�. doi: 10.1073/pnas.0907191107

Mazyadr, A. A., Khederr, A. A., El-Attart, A. K., Amer, W., Ismail, M. H., and Amal, A. F. (2014). Characterization of strawberry latent ringspot virzs (SLRSV) on strawberry in Egypt. Egypt. J. Virol. 11, 229�.

Min, B.-E., Feldman, T. S., Ali, A., Wiley, G., Muthukumar, V., Roe, B. A., et al. (2012). Molecular characterization, ecology, and epidemiology of a novel Tymovirus in Asclepias viridis from Oklahoma. Phytopathology 102, 166�. doi: 10.1094/PHYTO-05-11-0154

Morsy, M. R., Oswald, J., He, J., Tang, Y., and Roossinck, M. J. (2010). Teasing apart a three-way symbiosis: transcriptome analyses of Curvularia protuberata in response to viral infection and heat stress. Biochem. Biophys. Res. Commun. 401, 225�. doi: 10.1016/j.bbrc.2010.09.034

Murad, L., Bielawski, J. P., Matyasek, R., Kovarik, A., Nichols, R. A., Leitch, A. R., et al. (2004). The origin and evolution of geminivirus-related DNA sequences in Nicotiana. Heredity 92, 352�. doi: 10.1038/sj.hdy.6800431

Nag, D. K., Brecher, M., and Kramer, L. D. (2016). DNA forms of arboviral RNA genomes are generated following infection in mosquito cell cultures. Virology 498, 164�. doi: 10.1016/j.virol.2016.08.022

Nakatsukasa-Akune, M., Yamashita, K., Shimoda, Y., Uchiumi, T., Abe, M., Aoki, T., et al. (2005). Suppression of root nodule formation by artificial expression of the TrEnodDR1 (coat protein of White clover cryptic virus 1) gene in Lotus japonicus. Mol. Plant Microbe Interact. 18, 1069�. doi: 10.1094/MPMI-18-1069

Natsuaki, T., Natsuaki, K. T., Okuda, S., Teranaka, M., Milne, R. G., Boccardo, G., et al. (1986). Relationships between the cryptic and temperate viruses of alfalfa, beet and white clover. Intervirology 25, 69�. doi: 10.1159/000149658

Ndowora, T., Dahal, G., LaFleur, D., Harper, G., Hull, R., Olszewski, N. E., et al. (1999). Evidence that badnavirus infection in Musa can originate from integrated pararetroviral sequences. Virology 255, 214�. doi: 10.1006/viro.1998.9582

Nemchinov, L., and Hadidi, A. (1998). Apricot latent virus: a novel stone fruit pathogen and its relationship to apple stem pitting virus. Acta Horti. 472, 159�.

Nemchinov, L. G., Shamloul, A. M., Zemtchik, E. Z., Verderevskaya, T. D., and Hadidi, A. (2000). Apricot latent virus: a new species in the genus Foveavirus. Arch. Virol. 145, 1801�. doi: 10.1007/s007050070057

Nuss, D. L. (2008). “Hypoviruses,” in Encyclopedia of Virology, eds A. Granoff and R. Webster (Amsterdam: Elsevier), 580�. doi: 10.1016/b978-012374410-4.00406-4

Owens, R. A., Flores, R., Di Serio, F., Li, S., Pallas, V., and Randles, J. W. (2012). Virus Taxonomy: Ninth Report of the International Committee on Taxonomy of Viruses. Amsterdam: Elsevier.

Ozeki, J., Takahashi, S., Komatsu, K., Kagiwada, S., Yamashita, K., Mori, T., et al. (2006). A single amino acid in the RNA dependent RNA polymerase of Plantago asiatica mosaic virus contributes to systemic necrosis. Arch. Virol. 151, 2067�. doi: 10.1007/s00705-006-0766-3

Pagán, I., González-Jara, P., Moreno-Letelier, A., Rodelo-Urrego, M., Fraile, A., Pi༞ro, D., et al. (2012). Effect of biodiversity changes in disease risk: exploring disease emergence in a plant-virus system. PLoS Pathog. 8:e1002796. doi: 10.1371/journal.ppat.1002796

Pooggin, B. B. (2018). Small RNA-Omics for plant virus identification, virome reconstruction, and antiviral defense characterization. Front. Microbiol. 9:2779. doi: 10.3389/fmicb.2018.02779

Rrg, L. (2014). How to live with the enemy: understanding tolerance to parasites. PLoS Biol. 12:e1001989. doi: 10.1371/journal.pbio.1001989

Redman, R. S., Sheehan, K. B., Stout, R. G., Rodriguez, R. J., and Henson, J. M. (2002). Thermotholerance generated by plant/fungal symbiosis. Science 298:1581. doi: 10.1126/science.1072191

Richert-Pöggeler, K. R., and Minarovits, J. (2014). Diversity of latent plant-virus interactions and their impact on the virosphere. Plant Virus Host Interact. 14, 263�. doi: 10.1016/b978-0-12-411584-2.00014-7

Richert-Pöggeler, K. R., Noreen, F., Schwarzacher, T., Harper, G., and Hohn, T. (2003). Induction of infectious Petunia vein clearing (pararetro) virus from endogenous provirus in petunia. EMBO J. 22, 4836�. doi: 10.1093/emboj/cdg443

Richins, R. D., and Shepherd, R. J. (1986). Horseradish latent virus, a new member of the Caulimovirus group. Phytopathology 76, 749�.

Rodríguez-Nevado, C., Montes, N., and Pagán, I. (2017). Ecological factors affecting infection risk and population genetic diversity of a novel potyvirus in its native wild ecosystem. Front. Plant Sci. 8:1958. doi: 10.3389/fpls.2017.01958

Roossinck, M. J. (2005). Symbiosis versus competition in plant virus evolution. Nat. Rev. Microbiol. 3, 917�. doi: 10.1038/nrmicro1285

Roossinck, M. J. (2010). Lifestyles of plant viruses. Philos. Trans. R. Soc. Lond. B Biol. Sci. 365, 1899�. doi: 10.1098/rstb.2010.0057

Roossinck, M. J. (2011a). The big unknown: plant virus biodiversity. Curr. Opin. Virol. 1, 63�. doi: 10.1016/j.coviro.2011.05.022

Roossinck, M. J. (2011b). The good viruses: viral mutualistic symbioses. Nat. Rev. Microbiol. 9, 99�. doi: 10.1038/nrmicro2491

Roossinck, M. J. (2012a). “Persistent plant viruses: molecular hitchhikers or epigenetic elements,” in In Viruses: Essential Agents of Life, ed. G. Witzany (New York, NY: Springer), 177�. doi: 10.1007/978-94-007-4899-6_8

Roossinck, M. J. (2012b). Plant virus metagenomics: biodiversity and ecology. Annu. Rev. Genet. 46, 359�. doi: 10.1146/annurev-genet-110711-155600

Roossinck, M. J. (2013). Plant virus ecology. PLoS Pathog. 9:e1003304. doi: 10.1371/journal.ppat.1003304

Roossinck, M. J. (2015a). Metagenomics of plant and fungal viruses reveals an abundance of persistent lifestyles. Front. Microbiol. 12:767. doi: 10.3389/fmicb.2014.00767

Roossinck, M. J. (2015b). Move over, bacteria! Viruses make their mark as mutualistic microbial symbionts. J. Virol. 89, 6532�. doi: 10.1128/JVI.02974-14

Roossinck, M. J., and Garcia-Arenal, F. (2015). Ecosystem simplification, biodiversity loss and plant virus emergence. Curr. Opin. Virol. 10, 56�. doi: 10.1016/j.coviro.2015.01.005

Roossinck, M. J., Sabanadzovic, S., Okada, R., and Valverde, R. A. (2011). The remarkable evolutionary history of endornaviruses. J. Gen. Virol. 92, 2674�. doi: 10.1099/vir.0.034702-0

Rubino, L., and Russo, M. (1997). Molecular analysis of the pothos latent virus genome. J. Gen. Virol. 78, 1219�. doi: 10.1099/0022-1317-78-6-1219

Sabanadzovic, S., Valverde, R. A., Brown, J. K., Martin, R. R., and Tzanetakis, I. E. (2009). Southern tomato virus: the link between the families Totiviridae and Partitiviridae. Virus Res. 140, 130�. doi: 10.1016/j.virusres.2008.11.018

Safari, M., Ferrari, M. J., and Roossinck, M. J. (2019). Manipulation of aphid behavior by a persistent plant virus. J. Virol. 93:e01781-18. doi: 10.1128/JVI.01781-18

Schmelzer, K. (1969). Strawberry latent ringspot virus in Euonymous, Acacia, and Aesculus. Phytopathol. Z. 66, 1�.

Shapiro, L. R., Salvaudon, L., Mauck, K. E., Pulido, H., DeMoraes, C. M., Stephenson, A. G., et al. (2013). Disease interactions in a shared host plant: effects of pre-existing viral infection on cucurbit plant defense responses and resistance to bacterial wilt disease. PLoS One 8:e77393. doi: 10.1371/journal.pone.0077393

Shates, T. M., Sun, P., Malmstrom, C. M., Dominguez, C., and Mauck, K. E. (2019). Addressing research needs in the field of plant virus ecology by defining knowledge gaps and developing wild dicot study systems. Front. Microbiol. 9:3305. doi: 10.3389/fmicb.2018.03305

Solovyev, A. G., Novikov, V. K., Merits, A., Savenkov, E. I., Zelenina, D. A., Tyulkina, L. G., et al. (1994). Genome characterization and taxonomy of Plantago asiatica mosaic potexvirus. J. Gen. Virol. 75, 259�. doi: 10.1099/0022-1317-75-2-259

Song, D., Cho, W. K., Park, S.-H., Jo, Y., and Kim, K.-H. (2013). Evolution of and horizontal gene transfer in the Endornavirus genus. PLoS One 8:e64270. doi: 10.1371/journal.pone.0064270

Staginnus, C., Gregor, W., Mette, M. F., Teo, C. H., Borroto-Fernández, E. G., da Câmara Machado, M. L., et al. (2007). Endogenous pararetroviral sequences in tomato (Solanum lycopersicum) and related species. BMC Plant Biol. 7:24. doi: 10.1186/1471-2229-7-24

Staginnus, C., Iskra-Caruana, M., Lockhart, B., Hohn, T., and Richert-Pöggeler, K. R. (2009). Suggestions for a nomenclature of endogenous pararetroviral sequences in plants. Arch. Virol. 154, 1189�. doi: 10.1007/s00705-009-0412-y

Staginnus, C., and Richert-Pöggeler, K. R. (2006). Endogenous pararetroviruses: two-faced travelers in the plant genome. Trends Plant Sci. 11, 485�. doi: 10.1016/j.tplants.2006.08.008

Stobbe, A. H., and Roossinck, M. J. (2014). Plant virus metagenomics: what we know and why we need to know more. Front. Plant Sci. 5:150. doi: 10.3389/fpls.2014.00150

Susi, H., Filloux, D., Frilander, M. J., Roumagnac, P., and Laine, A.-L. (2019). Diverse and variable virus communities in wild plant populations revealed by metagenomic tools. Peer J. 7:e6140. doi: 10.7717/peerj.6140

Susi, H., Laine, A. L., Filloux, D., Kraberger, S., Farkas, K., Bernardo, P., et al. (2017). Genome sequences of a capulavirus infecting Plantago lanceolata in the Åland archipelago of Finland. Arch. Virol. 162, 2041�. doi: 10.1007/s00705-017-3298-0

Tang, J., Ward, L. I., and Clover, G. R. G. (2013). The diversity of strawberry latent ringspot virus in New Zealand. Plant Dis. 97, 662�. doi: 10.1094/PDIS-07-12-0703-RE

Tanne, E., and Sela, I. (2005). Occurrence of a DNA sequence of a non-retro RNA virus in a host plant genome and its expression: evidence for recombination between viral and host RNAs. Virology 332, 614�. doi: 10.1016/j.virol.2004.11.007

Teycheney, P.-Y., and Geering, A. D. W. (2011). 𠇎ndogenous viral sequences in plant genomes,” in Recent Advances in Plant Virology, eds C. Caranta, M. A. Aranda, M. Tepfer, and J. J. López-Moya (Caister: Academic Press), 343�.

Tripathi, J. N., Ntui, V. O., Ron, M., Muiruri, S. K., Britt, A., and Tripathi, L. (2019). CRISPR/Cas9 editing of endogenous banana streak virus in the B genome of Musa spp. overcomes a major challenge in banana breeding. Commun. Biol. 2:46. doi: 10.1038/s42003-019-0288-7

Urayama, S., Moriyama, H., Aoki, N., Nakazawa, Y., Okada, R., Kiyota, E., et al. (2010). Knock-down of OsDCL2 in rice negatively affects maintenance of the endogenous dsRNA virus, Oryza sativa endornavirus. Plant Cell Physiol. 51, 58�. doi: 10.1093/pcp/pcp167

Vaira, A. M., Maroon-Lango, C. J., and Hammond, J. (2008). Molecular characterization of Lolium latent virus, proposed type member of a new genus in the family Flexiviridae. Arch. Virol. 153, 1263�. doi: 10.1007/s00705-008-0108-8

Valverde, R. A. (1985). Spring beauty latent virus: a new member of the bromovirus group. Phytopathology 75, 395�. doi: 10.1094/Phyto-75-395

van Molken, T., de Caluwe, H., Hordijk, C. A., Leon-Reyes, A., Snoeren, T. A., van Dam, N. M., et al. (2012). Virus infection decreases the attractiveness of white clover plants for a non-vectoring herbivore. Oecologia 170, 433�. doi: 10.1007/s00442-012-2322-z

Varsani, A., Roumagnac, P., Fuchs, M., Navas-Castillo, J., Moriones, E., Idris, A., et al. (2017). Capulavirus and Grablovirus: two new genera in the family Geminiviridae. Arch. Virol. 162, 1819�. doi: 10.1007/s00705-017-3268-6

Watanabe, T., Suzuki, N., Tomonaga, K., Sawa, H., Matsuura, Y., Kawaguchi, Y., et al. (2019). Neo-virology: the raison d𠆞tre of viruses. Virus Res. 274:197751. doi: 10.1016/j.virusres.2019.197751

Westwood, J. H., McCann, L., Naish, M., Dixon, H., Murphy, A. M., Stancombe, M. A., et al. (2013). A viral RNA silencing suppressor interferes with abscisic acid-mediated signalling and induces drought tolerance in Arabidopsis thaliana. Mol. Plant Pathol. 14, 158�. doi: 10.1111/j.1364-3703.2012.00840.x

Wren, J. D., Roossinck, M. J., Nelson, R. S., Scheets, K., Palmer, M. W., and Melcher, U. (2006). Plant virus biodiversity and ecology. PLoS Biol. 4:e80. doi: 10.1371/journal.pbio.0040080

Xie, W. S., Antoniw, J. F., White, R. F., and Jolliffee, T. H. (1994). Effects of beet cryptic virus infection on sugar beet in field trials. Ann. Appl. Biol. 124, 451�. doi: 10.1111/j.1744-7348.1994.tb04150.x

Xu, P., Chen, F., Mannas, J. P., Feldman, T., Sumner, L. W., and Roossinck, M. J. (2008). Virus infection improves drought tolerance. New Phytol. 180, 911�. doi: 10.1111/j.1469-8137.2008.02627.x

Zemtchik, E. Z., and Verderevskaya, T. D. (1993). Latent virus on apricot unknown under Moldavian conditions. Russian Agric. Biol. 3, 130�.

Zhang, Y.-Z., Shi, M., and Holmes, E. C. (2018). Using metagenomics to characterize an expanding virosphere. Cell 172, 1168�. doi: 10.1016/j.cell.2018.02.043

Keywords : beneficial interactions with plant viruses, endogenous viral elements, latent infection, stress tolerance, plant virus

Citation: Takahashi H, Fukuhara T, Kitazawa H and Kormelink R (2019) Virus Latency and the Impact on Plants. Front. Microbiol. 10:2764. doi: 10.3389/fmicb.2019.02764

Received: 12 August 2019 Accepted: 12 November 2019
Published: 06 December 2019.

Jesús Navas-Castillo, Institute of Subtropical and Mediterranean Hortofruticultura La Mayora (IHSM), Spain

Israel Pagan, Polytechnic University of Madrid, Spain
Hanu R. Pappu, Washington State University, United States

Copyright © 2019 Takahashi, Fukuhara, Kitazawa and Kormelink. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.