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Review
. 2011 Jan;155(1):1-9.
doi: 10.1016/j.virusres.2010.10.003. Epub 2010 Oct 14.

Viral RNA silencing suppressors (RSS): novel strategy of viruses to ablate the host RNA interference (RNAi) defense system

Shalmali Bivalkar-Mehla  1 , Janaki Vakharia, Rajeev Mehla, Measho Abreha, Jagat Rakesh Kanwar, Akshay Tikoo, Ashok Chauhan
Affiliations
Review

Viral RNA silencing suppressors (RSS): novel strategy of viruses to ablate the host RNA interference (RNAi) defense system

Shalmali Bivalkar-Mehla et al. Virus Res. 2011 Jan.

Abstract

Pathogenic viruses have developed a molecular defense arsenal for their survival by counteracting the host anti-viral system known as RNA interference (RNAi). Cellular RNAi, in addition to regulating gene expression through microRNAs, also serves as a barrier against invasive foreign nucleic acids. RNAi is conserved across the biological species, including plants, animals and invertebrates. Viruses in turn, have evolved mechanisms that can counteract this anti-viral defense of the host. Recent studies of mammalian viruses exhibiting RNA silencing suppressor (RSS) activity have further advanced our understanding of RNAi in terms of host-virus interactions. Viral proteins and non-coding viral RNAs can inhibit the RNAi (miRNA/siRNA) pathway through different mechanisms. Mammalian viruses having dsRNA-binding regions and GW/WG motifs appear to have a high chance of conferring RSS activity. Although, RSSs of plant and invertebrate viruses have been well characterized, mammalian viral RSSs still need in-depth investigations to present the concrete evidences supporting their RNAi ablation characteristics. The information presented in this review together with any perspective research should help to predict and identify the RSS activity-endowed new viral proteins that could be the potential targets for designing novel anti-viral therapeutics.

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Figures

Figure 1
Figure 1. Schematic illustration of RSS activity of different viral proteins that inhibit the host RNAi pathway
Following transcription from miRNA genes in the nucleus, pri-miRNAs are processed to pre-miRNAs by Drosha. Exportin-5 facilitates the export of pre-miRNA into the cytoplasm where they are processed by Dicer/TRPB into mature miRNA. Dicer also processes the shRNAs transcribed from shRNA expression vectors into siRNA. The mature miRNA/siRNA guide strands are loaded on to RNA induced silencing complex (RISC). RISC targets the complementary mRNA transcripts. Viral RSS proteins inhibit the cellular RNAi pathway at different steps. Viral proteins NS1 of influenza virus and E3L of Vaccinia virus possess RNA binding domains, localize to the nucleus and suppress RNAi by sequestering the small RNA intermediates. HIV-1 Tat / PFV-1 Tas localize to the nucleus and possess RSS activity by interaction with the cytoplasmic Dicer protein. Tat and Tas may also act by sequestration of small RNAs similar to other viral proteins in the nucleus (shown as ?). Viral proteins NSs of LACV and VP35 of Ebola virus localize in the cytoplasm, possess RNA binding domains and suppress RNAi by sequestering the small RNA intermediates. HCV core and E2 proteins interact with Dicer and Ago2 proteins, respectively, in RISC to suppress RNAi.
Fig 2
Fig 2. HIV Tat expression
pcDNA-Tat plasmid transfection in SVGA (astrocytes) cells followed by immunostaining after 48h using Tat monoclonal antibody. (A) Tat expression was seen in the nucleus. (B) Hoechst nuclear staining of panel A.
Fig 3
Fig 3. Influenza A virus NS1 expression
pcDNA-NS1 plasmid transfection in N1E (neuroblastoma) cells followed by immunostaining after 48h using polyclonal NS1 antibody. (A) NS1 expression was seen in the nucleus. (B) Negative control with isotype antibody.
Fig 4
Fig 4. Viral RSS proteins possess GW/WG motif
The amino acid sequence of viral RSS proteins showing the presence of GW/WG motifs. GW/WG motif has been implicated in the interaction with Ago proteins and presence of this motif in viral RSS proteins may indicate their ability to interact with and inhibit Ago proteins involved in RNAi.
Fig 5
Fig 5
Three-D molecular modeling of HCV core protein: Protein modeling was performed by using I–TASSER server. Protein modeling of HCV core protein revealed GW/WG motifs on the surface and these may be potential binding sites with Ago proteins.
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References

    1. Ahluwalia JK, Khan SZ, Soni K, Rawat P, Gupta A, Hariharan M, Scaria V, Lalwani M, Pillai B, Mitra D, Brahmachari SK. Human cellular microRNA hsa-miR-29a interferes with viral nef protein expression and HIV-1 replication. Retrovirology. 2008;5:117. - PMC - PubMed
    1. Alvarado V, Scholthof HB. Plant responses against invasive nucleic acids: RNA silencing and its suppression by plant viral pathogens. Semin. Cell Dev. Biol. 2009;20(9):1032–1040. - PMC - PubMed
    1. Andersson MG, Haasnoot PC, Xu N, Berenjian S, Berkhout B, Akusjärvi G. Suppression of RNA interference by adenovirus virus-associated RNA. J. Virol. 2005;79(15):9556–9565. - PMC - PubMed
    1. Azevedo J, Garcia D, Pontier D, Ohnesorge S, Yu A, Garcia S, Braun L, Bergdoll M, Hakimi MA, Lagrange T, Voinnet O. Argonaute quenching and global changes in Dicer homeostasis caused by a pathogen-encoded GW repeat protein. Genes Dev. 2010;24(9):904–915. - PMC - PubMed
    1. Bannert H, Muranyi W, Ogryzko VV, Nakatani Y, Flügel RM. Co-activators p300 and PCAF physically and functionally interact with the foamy viral trans-activator. BMC Mol. Biol. 2004;5:16. - PMC - PubMed

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