siRNA targeting vaccinia virus double-stranded RNA binding protein [E3L] exerts potent antiviral effects.
The Vaccinia virus gene, E3L, encodes a double-stranded RNA [dsRNA]-binding protein. We hypothesized that, owing to the critical nature of dsRNA in triggering host innate antiviral responses, E3L-specific small-interfering RNAs [siRNAs] should be effective antiviral agents against pox viruses, for which Vaccinia virus is an appropriate surrogate. In this study, we have utilized two human cell types, namely, HeLa and 293T, one which responds to interferon [IFN]-beta and the other produces and responds to IFN-beta, respectively. The antiviral effects were equally robust in HeLa and 293T cells. However, in the case of 293T cells, several distinct features were observed, when IFN-beta is activated in these cells. Vaccinia virus replication was inhibited by 97% and 98% as compared to control infection in HeLa and 293T cells transfected with E3L-specific siRNAs, respectively. These studies demonstrate the utility of E3L-specific siRNAs as potent antiviral agents for small pox and related pox viruses.
Dave
Rajnish S
RS
The Dorrance H. Hamilton Laboratories, Division of Infectious Diseases, Center for Human Virology, Thomas Jefferson University, Philadelphia, PA 19107, USA. rajnish.dave@jefferson.edu
McGettigan
James P
JP
Qureshi
Tazeen
T
Schnell
Matthias J
MJ
Nunnari
Giuseppe
G
Pomerantz
Roger J
RJ
D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D002460:Cell Line; D015536:Down-Regulation; D005814:Genes, Viral; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000235:genetics; D007370:Interferon Type I / Q000494:pharmacology; D016899:Interferon-beta / Q000096:biosynthesis; D008954:Models, Biological; D034741:RNA, Small Interfering / Q000235:genetics* / Q000494:pharmacology*; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D011994:Recombinant Proteins; D014158:Transcription, Genetic; D014162:Transfection; D014616:Vaccinia virus / Q000187:drug effects* / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D012901:Variola virus / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; C081374:E3L protein, Vaccinia virus; D007370:Interferon Type I; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D014764:Viral Proteins; D016899:Interferon-beta