SV40-encoded microRNAs regulate viral gene expression and reduce susceptibility to cytotoxic T cells

Abstract

MicroRNAs (miRNAs) are small (approximately 22-nucleotide) RNAs that in lower organisms serve important regulatory roles in development and gene expression, typically by forming imperfect duplexes with target messenger RNAs. miRNAs have also been described in mammalian cells and in infections with Epstein-Barr virus (EBV), but the function of most of them is unknown. Although one EBV miRNA probably altered the processing of a viral mRNA, the regulatory significance of this event is uncertain, because other transcripts exist that can supply the targeted function. Here we report the identification of miRNAs encoded by simian virus 40 (SV40) and define their functional significance for viral infection. SVmiRNAs accumulate at late times in infection, are perfectly complementary to early viral mRNAs, and target those mRNAs for cleavage. This reduces the expression of viral T antigens but does not reduce the yield of infectious virus relative to that generated by a mutant lacking SVmiRNAs. However, wild-type SV40-infected cells are less sensitive than the mutant to lysis by cytotoxic T cells, and trigger less cytokine production by such cells. Thus, viral evolution has taken advantage of the miRNA pathway to generate effectors that enhance the probability of successful infection.

MicroRNAs in the regulation of TLR and RIG-I pathways

“…MiRNAs encoded by simian virus 40, accumulate at late times and perfectly target viral T antigen mRNAs without reducing the infectious viral yield. 118 Thus, viruses lacking the expression of these viral antigens display decreased sensitivity to cytotoxic T cell lysis and decreased cytokine production. Viral BamHI A rightward transcripts miRNA, encoded by EBV, targets the EBV latency associated membrane protein 1, a transforming protein, which resulted in decreased apoptosis of infected cells.…”

Anti-miRNA oligonucleotides (AMOs): ammunition to target miRNAs implicated in human disease?

“…This was demonstrated for miRNAs derived from the circular dsDNA simian virus 40 (SV40), which are perfectly complementary to the early viral mRNA coding for T antigen and accumulate in the late stages during infection. 41 The reduced expression of this nonstructural protein renders the infected cells less sensitive to lysis by cytotoxic T cells.…”

La bataille du silence

“…Cette découverte a des implications fondamentales en santé humaine et vétérinaire car ces miARN viraux semblent jouer un rôle très important, non seulement dans l'expression des génomes viraux, mais aussi dans l'établissement d'un terrain favorable à l'infection. Par exemple, cette usurpation de la voie miARN de l'hôte s'illustre dans le cas du virus SV40 par l'élimination de ses transcrits précoces, produisant l'antigène T, par des miARN viraux codés par son génome, lui permettant ainsi de contourner le système immunitaire [57]. Il est enfin très probable que les patrons cellulaires de miARN de l'hôte jouent un rôle non négligeable dans le tropisme tissulaire de certains virus de vertébrés, comme cela a été démontré avec le virus de l'hépatite C et le rétrovirus foamy des primates [58][59][60].…”