Viral Suppressor Of RNA Interference Research Articles

Live-attenuated virus vaccine defective in RNAi suppression induces rapid protection in neonatal and adult mice lacking mature B and T cells

Global control of infectious diseases depends on the continuous development and deployment of diverse vaccination strategies. Currently available live-attenuated and killed virus vaccines typically take a week or longer to activate specific protection by the adaptive immunity. The mosquito-transmitted Nodamura virus (NoV) is attenuated in mice by mutations that prevent expression of the B2 viral suppressor of RNA interference (VSR) and consequently, drastically enhance in vivo production of the virus-targeting small-interfering RNAs. We reported recently that 2 d after immunization with live-attenuated VSR-disabled NoV (NoVΔB2), neonatal mice become fully protected against lethal NoV challenge and develop no detectable infection. Using Rag1-/- mice that produce no mature B and T lymphocytes as a model, here we examined the hypothesis that adaptive immunity is dispensable for the RNAi-based protective immunity activated by NoVΔB2 immunization. We show that immunization of both neonatal and adult Rag1-/- mice with live but not killed NoVΔB2 induces full protection against NoV challenge at 2 or 14 d postimmunization. Moreover, NoVΔB2-induced protective antiviral immunity is virus-specific and remains effective in adult Rag1-/- mice 42 and 90 d after a single-shot immunization. We conclude that immunization with the live-attenuated VSR-disabled RNA virus vaccine activates rapid and long-lasting protective immunity against lethal challenges by a distinct mechanism independent of the adaptive immunity mediated by B and T cells. Future studies are warranted to determine whether additional animal and human viruses attenuated by VSR inactivation induce similar protective immunity in healthy and adaptive immunity-compromised individuals.

The subgenomic flaviviral RNA suppresses RNA interference through competing with siRNAs for binding RISC components.

During the life cycle of mosquito-borne flaviviruses, substantial subgenomic flaviviral RNA (sfRNA) is produced via incomplete degradation of viral genomic RNA by host XRN1. Zika virus (ZIKV) sfRNA has been detected in mosquito and mammalian somatic cells. Human neural progenitor cells (hNPCs) in the developing brain are the major target cells of ZIKV, and antiviral RNA interference (RNAi) plays a critical role in hNPCs. However, whether ZIKV sfRNA was produced in ZIKV-infected hNPCs as well as its function remains not known. In this study, we demonstrate that abundant sfRNA was produced in ZIKV-infected hNPCs. RNA pulldown and mass spectrum assays showed ZIKV sfRNA interacted with host proteins RHA and PACT, both of which are RNA-induced silencing complex (RISC) components. Functionally, ZIKV sfRNA can antagonize RNAi by outcompeting small interfering RNAs (siRNAs) in binding to RHA and PACT. Furthermore, the 3' stem loop (3'SL) of sfRNA was responsible for RISC components binding and RNAi inhibition, and 3'SL can enhance the replication of a viral suppressor of RNAi (VSR)-deficient virus in a RHA- and PACT-dependent manner. More importantly, the ability of binding to RISC components is conversed among multiple flaviviral 3'SLs. Together, our results identified flavivirus 3'SL as a potent VSR in RNA format, highlighting the complexity in virus-host interaction during flavivirus infection.IMPORTANCEZika virus (ZIKV) infection mainly targets human neural progenitor cells (hNPCs) and induces cell death and dysregulated cell-cycle progression, leading to microcephaly and other central nervous system abnormalities. RNA interference (RNAi) plays critical roles during ZIKV infections in hNPCs, and ZIKV has evolved to encode specific viral proteins to antagonize RNAi. Herein, we first show that abundant sfRNA was produced in ZIKV-infected hNPCs in a similar pattern to that in other cells. Importantly, ZIKV sfRNA acts as a potent viral suppressor of RNAi (VSR) by competing with siRNAs for binding RISC components, RHA and PACT. The 3'SL of sfRNA is responsible for binding RISC components, which is a conserved feature among mosquito-borne flaviviruses. As most known VSRs are viral proteins, our findings highlight the importance of viral non-coding RNAs during the antagonism of host RNAi-based antiviral innate immunity.

Parallel evolution and enhanced virulence upon in vivo passage of an RNA virus in Drosophila melanogaster.

Virus evolution is strongly affected by antagonistic co-evolution of virus and host. Host immunity positively selects for viruses that evade the immune response, which in turn may drive counter-adaptations in host immune genes. We investigated how host immune pressure shapes virus populations, using the fruit fly Drosophila melanogaster and its natural pathogen Drosophila C virus (DCV), as a model. We performed an experimental evolution study in which DCV was serially passaged for ten generations in three fly genotypes differing in their antiviral RNAi response: wild-type flies and flies in which the endonuclease gene Dicer-2 was either overexpressed or inactivated. All evolved virus populations replicated more efficiently in vivo and were more virulent than the parental stock. The number of polymorphisms increased in all three host genotypes with passage number, which was most pronounced in Dicer-2 knockout flies. Mutational analysis showed strong parallel evolution, as mutations accumulated in a specific region of the VP3 capsid protein in every lineage in a host genotype-independent manner. The parental tyrosine at position ninety-five of VP3 was substituted with either one of five different amino acids in fourteen out of fifteen lineages. However, no consistent amino acid changes were observed in the viral RNAi suppressor gene 1A, nor elsewhere in the genome in any of the host backgrounds. Our study indicates that the RNAi response restricts the sequence space that can be explored by viral populations. Moreover, our study illustrates how evolution towards higher virulence can be a highly reproducible, yet unpredictable process.

P4 protein of an Indian isolate of rice tungro bacilliform virus modulates gene silencing.

Plant hosts and their viral pathogens are engaged in a constant cycle of defense and counter-defense as part of a molecular arms race, principal among them being the plant RNAi defense and the viral RNAi suppressor counter-defense. Rice tungro bacilliform virus (RTBV), member of the family Caulimoviridae, genus Tungrovirus, species Tungrovirus oryzae, infects rice in South- and Southeast Asia and causes severe symptoms of stunting, yellow-orange discoloration and twisting of leaf tips. To better understand the possible counter-defensive roles of RTBV against the host RNAi defense system, we explored the ability of the P4 protein of an Indian isolate of RTBV to act as a possible modulator of RNAi. Using a transient silencing and silencing suppression assay in Nicotiana benthamiana, we show that P4 not only displays an RNAi suppressor function, but also potentially enhances RNAi. The results also suggests that the N-terminal 168 amino acid residues of P4 are sufficient to maintain RNAi suppressor activity. Taken together with the earlier reports this work strengthens the view that the P4 protein carries out RNAi suppressor and a potential RNAi enhancer function.

Alphavirus infection triggers antiviral RNAi immunity in mammals

RNA interference (RNAi) is a well-established antiviral immunity. However, for mammalian somatic cells, antiviral RNAi becomes evident only when viral suppressors of RNAi (VSRs) are disabled by mutations or VSR-targeting drugs, thereby limiting its scope as a mammalian immunity. We find that a wild-type alphavirus, Semliki Forest virus (SFV), triggers the Dicer-dependent production of virus-derived small interfering RNAs (vsiRNAs) in both mammalian somatic cells and adult mice. These SFV-vsiRNAs are located at a particular region within the 5' terminus of the SFV genome, Argonaute loaded, and active in conferring effective anti-SFV activity. Sindbis virus, another alphavirus, also induces vsiRNA production in mammalian somatic cells. Moreover, treatment with enoxacin, an RNAi enhancer, inhibits SFV replication dependent on RNAi response invitro and invivo and protects mice from SFV-induced neuropathogenesis and lethality. These findings show that alphaviruses trigger the production of active vsiRNA in mammalian somatic cells, highlighting the functional importance and therapeutic potential of antiviral RNAi in mammals.

Infection Defects of RNA and DNA Viruses Induced by Antiviral RNA Interference.

Immune recognition of viral genome-derived double-stranded RNA (dsRNA) molecules and their subsequent processing into small interfering RNAs (siRNAs) in plants, invertebrates, and mammals trigger specific antiviral immunity known as antiviral RNA interference (RNAi). Immune sensing of viral dsRNA is sequence-independent, and most regions of viral RNAs are targeted by virus-derived siRNAs which extensively overlap in sequence. Thus, the high mutation rates of viruses do not drive immune escape from antiviral RNAi, in contrast to other mechanisms involving specific virus recognition by host immune proteins such as antibodies and resistance (R) proteins in mammals and plants, respectively. Instead, viruses actively suppress antiviral RNAi at various key steps with a group of proteins known as viral suppressors of RNAi (VSRs). Some VSRs are so effective in virus counter-defense that potent inhibition of virus infection by antiviral RNAi is undetectable unless the cognate VSR is rendered nonexpressing or nonfunctional. Since viral proteins are often multifunctional, resistance phenotypes of antiviral RNAi are accurately defined by those infection defects of VSR-deletion mutant viruses that are efficiently rescued by host deficiency in antiviral RNAi. Here, we review and discuss in vivo infection defects of VSR-deficient RNA and DNA viruses resulting from the actions of host antiviral RNAi in model systems.

RNA interference, an emerging component of antiviral immunity in mammals.

Antiviral RNA interference (RNAi) is an immune pathway that can, in certain conditions, protect mammalian cells against RNA viruses. It depends on the recognition and dicing of viral double-stranded RNA by a protein of the Dicer family, which leads to the production of viral small interfering RNAs (vsiRNAs) that sequence-specifically guide the degradation of cognate viral RNA. If the first line of defence against viruses relies on type-I and type-III interferons (IFN) in mammals, certain cell types such as stem cells, that are hyporesponsive for IFN, instead use antiviral RNAi via the expression of a specific antiviral Dicer. In certain conditions, antiviral RNAi can also contribute to the protection of differentiated cells. Indeed, abundant vsiRNAs are detected in infected cells and efficiently guide the degradation of viral RNA, especially in cells infected with viruses disabled for viral suppressors of RNAi (VSRs), which are virally encoded blockers of antiviral RNAi. The existence and importance of antiviral RNAi in differentiated cells has however been debated in the field, because data document mutual inhibition between IFN and antiviral RNAi. Recent developments include the engineering of a small molecule inhibitor of VSR to probe antiviral RNAi in vivo, as well as the detection of vsiRNAs inside extracellular vesicles in the serum of infected mice. It suggests that using more complex, in vivo models could allow to unravel the contribution of antiviral RNAi to immunity at the host level.

Suppressors of silencers: Exploring viral suppression of RNAi in emerging RNA viruses

The primary objective of this review is to describe the various mechanisms of RNA interference (RNAi) suppression in emerging RNA viruses. A search was conducted using MeSH terms such as “emerging RNA viruses,” “RNA interference,” “RNAi suppression in West Nile virus, SARS-CoV, MERS-CoV, SARS-CoV-2, Ebola virus, H1N1, and Zika virus,” “viral suppressors of RNAi in West Nile virus, SARS-CoV, MERS-CoV, SARS-CoV-2, Ebola virus, H1N1, and Zika virus,” and “siRNA prophylaxis and treatment for emerging viruses” in PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar databases. The inclusion criteria for this review encompass articles published in English between 2000 and 2023 on RNAi suppression in emerging viruses. Excluded were studies that inhibited viral replication through methods other than RNAi suppression. Viral suppressors of RNAi (VSR) typically silence RNAi by binding to viral double-stranded RNA intermediate and small interfering RNA (siRNA). Zika virus and coronaviruses execute RNAi suppression through VSR interactions with RNA. However, unique mechanisms of RNAi suppression were observed in West Nile virus (WNV), Ebola virus, and Influenza A–H1N1. In WNV, a unique protein-RNA interaction was noted, wherein subgenomic RNA directly interacts with Dicer to inhibit RNAi. In Ebola and the H1N1 virus, protein–protein interactions are employed to silence RNAi. VP35 of the Ebola virus binds to Dicer partner proteins, TAR-RNA binding protein (TRBP), and protein activator of protein kinase R (PACT ), while the nonstructural protein 1 (NS1) of H1N1 binds to TRBP to suppress RNAi. Several research studies have demonstrated that by varying the delivery and dosage of siRNAs, they can be used as tools to effectively hinder the replication of emerging viruses in both cell cultures and animal models. Therefore, siRNAs can be used for prophylaxis and postexposure treatment of these viruses. Currently, no vaccines or antivirals exist for many emerging viruses, which employ diverse mechanisms to suppress RNAi. Nevertheless, siRNAs provide an attractive novel tool for prophylactic and postexposure treatment of these viruses.

Mouse circulating extracellular vesicles contain virus-derived siRNAs active in antiviral immunity.

Induction and suppression of antiviral RNA interference (RNAi) has been observed in mammals during infection with at least seven distinct RNA viruses, including some that are pathogenic in humans. However, while the cell-autonomous immune response mediated by antiviral RNAi is gradually being recognized, little is known about systemic antiviral RNAi in mammals. Furthermore, extracellular vesicles (EVs) also function in viral signal spreading and host immunity. Here, we show that upon antiviral RNAi activation, virus-derived small-interfering RNAs (vsiRNAs) from Nodamura virus (NoV), Sindbis virus (SINV), and Zika virus (ZIKV) enter the murine bloodstream via EVs for systemic circulation. vsiRNAs in the EVs are biologically active, since they confer RNA-RNA homology-dependent antiviral activity in both cultured cells and infant mice. Moreover, we demonstrate that vaccination with a live-attenuated virus, rendered deficient in RNAi suppression, induces production of stably maintained vsiRNAs and confers protective immunity against virus infection in mice. This suggests that vaccination with live-attenuated VSR (viral suppressor of RNAi)-deficient mutant viruses could be a new strategy to induce immunity.

BmNPV p35 Reduces the Accumulation of Virus-Derived siRNAs and Hinders the Function of siRNAs to Facilitate Viral Infection.

Antiviral immunity involves various mechanisms and responses, including the RNA interference (RNAi) pathway. During long-term coevolution, viruses have gained the ability to evade this defense by encoding viral suppressors of RNAi (VSRs). It was reported that p35 of baculovirus can inhibit cellular small interference RNA (siRNA) pathway; however, the molecular mechanisms underlying p35 as a VSR remain largely unclear. Here, we showed that p35 of Bombyx mori nucleopolyhedrovirus (BmNPV) reduces the accumulation of virus-derived siRNAs (vsiRNAs) mapped to a particular region in the viral genome, leading to an increased expression of the essential genes in this region, and revealed that p35 disrupts the function of siRNAs by preventing them from loading into Argonaute-2 (Ago2). This repressive effect on the cellular siRNA pathway enhances the replication of BmNPV. Thus, our findings illustrate for the first time the inhibitory mechanism of a baculovirus VSR and how this effect influences viral infection.

Antiviral RNA interference in disease vector (Asian longhorned) ticks.

Disease vectors such as mosquitoes and ticks play a major role in the emergence and re-emergence of human and animal viral pathogens. Compared to mosquitoes, however, much less is known about the antiviral responses of ticks. Here we showed that Asian longhorned ticks (Haemaphysalis longicornis) produced predominantly 22-nucleotide virus-derived siRNAs (vsiRNAs) in response to severe fever with thrombocytopenia syndrome virus (SFTSV, an emerging tick-borne virus), Nodamura virus (NoV), or Sindbis virus (SINV) acquired by blood feeding. Notably, experimental acquisition of NoV and SINV by intrathoracic injection also initiated viral replication and triggered the production of vsiRNAs in H. longicornis. We demonstrated that a mutant NoV deficient in expressing its viral suppressor of RNAi (VSR) replicated to significantly lower levels than wildtype NoV in H. longicornis, but accumulated to higher levels after knockdown of the tick Dicer2-like protein identified by phylogeny comparison. Moreover, the expression of a panel of known animal VSRs in cis from the genome of SINV drastically enhanced the accumulation of the recombinant viruses. This study establishes a novel model for virus-vector-mouse experiments with longhorned ticks and provides the first in vivo evidence for an antiviral function of the RNAi response in ticks. Interestingly, comparing the accumulation levels of SINV recombinants expressing green fluorescent protein or SFTSV proteins identified the viral non-structural protein as a putative VSR. Elucidating the function of ticks’ antiviral RNAi pathway in vivo is critical to understand the virus-host interaction and the control of tick-borne viral pathogens.

Unlocking the therapeutic potential of antiviral RNAi

RNA interference (RNAi) provides antiviral defense in many organisms, including plants, insects, and nematodes. In this issue of Immunity, Fang etal. (2021) utilize designer peptides targeting viral suppressors of RNAi to provide evidence for the relevance of RNAi to antiviral immunity in mammals, also revealing the potential of this approach toward antiviral therapy.

Inhibition of viral suppressor of RNAi proteins by designer peptides protects from enteroviral infection in vivo

RNA interference (RNAi) is the major antiviral mechanism in plants and invertebrates, but the absence of detectable viral (v)siRNAs in mammalian cells upon viral infection has questioned the functional relevance of this pathway in mammalian immunity. We designed a series of peptides specifically targeting enterovirus A71 (EV-A71)-encoded protein 3A, a viral suppressor of RNAi (VSR). These peptides abrogated the VSR function of EV-A71 in infected cells and resulted in the accumulation of vsiRNAs and reduced viral replication. These vsiRNAs were functional, as evidenced by RISC-loading and silencing of target RNAs. The effects of VSR-targeting peptides (VTPs) on infection with EV-A71 as well as another enterovirus, Coxsackievirus-A16, were ablated upon deletion of Dicer1 or AGO2, core components of the RNAi pathway. Invivo, VTP treatmentprotected mice against lethal EV-A71 challenge, with detectable vsiRNAs. Our findings provide evidencefor the functional relevance of RNAi in mammalian immunity and present a therapeutic strategy for infectious disease.

Ca2+ kickstarts antiviral RNAi

RNAi is a major plant antiviral strategy. However, the mechanisms triggering RNAi are unknown. In this issue of Cell Host & Microbe, Wang etal. (2021) demonstrate that wound-induced calcium signaling induces RNAi activation. As a counter-defense, a viral suppressor of RNAi (VSR) interferes with players in calcium signaling.

Construction of an Agrobacterium Mediated RNAI Genetic Transformation Vector Targeting the Replicase Gene of Indian cassava mosaic virus and Evaluation of Their Transformation Ability in Cassava Immature Leaf Lobes

Cassava mosaic virus is one of the major problems affecting cassava industry in India. Currently there are no effective strategy to completely protect cassava from cassava mosaic viruses. In order to attain cassava mosaic virus resistance RNAi vectors targeting the replicase gene of Indian cassava mosaic virus is constructed in this study. Their efficiency to transform cassava immature leaf lobes were also studied here. Replicase gene of Indian cassava mosaic virus in Tamilnadu are cloned and sequenced. Conserved domains are identified and sub cloned to CSIRO RNAi vector system and transformation studies are done in immature cassava leaves. Two different RNAi vectors were constructed, utilizing a conserved 440bp of 5’ end of ICMV Rep (AC1) gene which also corresponds to a part of AC4 gene, and functions as a viral RNAi suppressor protein. The partial Rep gene of ICMV was cloned in sense and anti-sense orientations in the RNAi intermediate vector, pHANNIBAL. After cloning into pHANNIBAL, the cloned RNAi gene cassettes of ICMV is released and cloned into the binary vector, pART27, which contains the kanamycin-resistance gene as a plant selectable marker. In order to use hygromycin as a selection agent in cassava genetic transformation, RNAi–Rep gene cassettes of ICMV were cloned into pCAMBIA1305.2. These constructs were named pICR1 and pICR2 respectively. The Genetic transformation studies in cassava leaves done using pICR2 vector could generate PCR positive plants. An agrobacterium mediated replicase RNAi vector is developed and that can be transformed into cassava immature leaf lobes. Their efficiency to silence the Indian cassava mosaic virus should be studied further.

The Capsid Protein of Rubella Virus Antagonizes RNA Interference in Mammalian Cells.

Rubella virus (RuV) is the infectious agent of a series of birth defect diseases termed congenital rubella syndrome, which is a major public health concern all around the world. RNA interference (RNAi) is a crucial antiviral defense mechanism in eukaryotes, and numerous viruses have been found to encode viral suppressors of RNAi (VSRs) to evade antiviral RNAi response. However, there is little knowledge about whether and how RuV antagonizes RNAi. In this study, we identified that the RuV capsid protein is a potent VSR that can efficiently suppress shRNA- and siRNA-induced RNAi in mammalian cells. Moreover, the VSR activity of the RuV capsid is dependent on its dimerization and double-stranded RNA (dsRNA)-binding activity. In addition, ectopic expression of the RuV capsid can effectively rescue the replication defect of a VSR-deficient virus or replicon, implying that the RuV capsid can act as a VSR in the context of viral infection. Together, our findings uncover that RuV encodes a VSR to evade antiviral RNAi response, which expands our understanding of RuV–host interaction and sheds light on the potential therapeutic target against RuV.

Elevated Carbon Dioxide Levels Decreases Cucumber Mosaic Virus Accumulation in Correlation with Greater Accumulation of rgs-CaM, an Inhibitor of a Viral Suppressor of RNAi.

Plant viruses cause a range of plant diseases symptoms that are often responsible for significant crop production losses and the severity and spread of the symptoms may be affected by climate change. While the increase in anthropogenic activities has caused a critical problem of increased CO2 levels in the atmosphere, these elevated CO2 levels have been reported to reduce virus disease severity in some plant species. In such instances, it is not clear if the plant defense mechanisms are being enhanced or virus-mediated mechanisms to overcome plant resistance are being defeated. Additionally, a few studies have been attempted in this area to determine if reduced disease is the norm or the exception under enhanced CO2 levels. In the present study, the effects of elevated CO2 levels (750 ppm vs. 390 ppm) on RNAi-mediated resistance of Nicotiana tabacum against the cucumber mosaic virus (CMV), and the activity of viral suppressor of RNAi (VSR) 2b protein of CMV were evaluated. On the one hand, our results showed that elevated CO2 decreased the transcription of dicer-like protein 2 (DCL2), DCL4, and argonaut 1 (AGO1) genes with functions related to RNAi-mediated resistance when infected by CMV, which is contradictory with the decreased CMV copy numbers under elevated CO2. On the other hand, we found that elevated CO2 increased the calcium concentration and expression of the calcium-binding protein rgs-CaM in tobacco plants when infected by CMV, which directly weakened the function of 2b protein, the VSR of CMV, and therefore decreased the infection efficiency of the virus and suppressed the severity of CMV in tobacco plants under elevated CO2. This study provides molecular insights into the ecological implications underlying the development of prevention strategies against plant virus infection in the context of climate change.

DNA Geminivirus Infection Induces an Imprinted E3 Ligase Gene to Epigenetically Activate Viral Gene Transcription.

Flowering plants and mammals contain imprinted genes that are primarily expressed in the endosperm and placenta in a parent-of-origin manner. In this study, we show that early activation of the geminivirus genes C2 and C3 in Arabidopsis (Arabidopsis thaliana) plants, encoding a viral suppressor of RNA interference and a replication enhancer protein, respectively, is correlated with the transient vegetative expression of VARIANT IN METHYLATION5 (VIM5), an endosperm imprinted gene that is conserved in diverse plant species. VIM5 is a ubiquitin E3 ligase that directly targets the DNA methyltransferases MET1 and CMT3 for degradation by the ubiquitin-26S proteasome proteolytic pathway. Infection with Beet severe curly top virus induced VIM5 expression in rosette leaf tissues, possibly via the expression of the viral replication initiator protein, leading to the early activation of C2 and C3 coupled with reduced symmetric methylation in the C2-3 promoter and the onset of disease symptoms. These findings demonstrate how this small DNA virus recruits a host imprinted gene for the epigenetic activation of viral gene transcription. Our findings reveal a distinct strategy used by plant pathogens to exploit the host machinery in order to inhibit methylation-mediated defense responses when establishing infection.

The 3A protein of coxsackievirus B3 acts as a viral suppressor of RNA interference

RNA interference (RNAi) is a potent antiviral defence mechanism in eukaryotes, and numerous viruses have been found to encode viral suppressors of RNAi (VSRs). Coxsackievirus B3 (CVB3) belongs to the genus Enterovirus in the family Picornaviridae, and has been reported to be a major causative pathogen for viral myocarditis. Despite the importance of CVB3, it is unclear whether CVB3 can also encode proteins that suppress RNAi. Here, we showed that the CVB3 nonstructural protein 3A suppressed RNAi triggered by either small hairpin RNAs (shRNAs) or small interfering RNAs (siRNAs) in mammalian cells. We further uncovered that CVB3 3A interacted directly with double-stranded RNAs (dsRNAs) and siRNAs in vitro. Through mutational analysis, we found that the VSR activity of CVB3 3A was significantly reduced by mutations of D24A/L25A/L26A, Y37A/C38A and R60A in conserved residues. In addition, the 3A protein encoded by coxsackievirus B5 (CVB5), another member of Enterovirus, also showed VSR activity. Taken together, our findings showed that CVB3 3A has in vitro VSR activity, thereby providing insights into the pathogenesis of CVB3 and other enteroviruses.

SARS-CoV-2-encoded nucleocapsid protein acts as a viral suppressor of RNA interference in cells

SARS-CoV-2-encoded nucleocapsid protein acts as a viral suppressor of RNA interference in cells