Small interfering RNAs targeting peste des petits ruminants virus M mRNA increase virus-mediated fusogenicity and inhibit viral replication in vitro

Antiviral Res. 2015 Nov:123:22-6. doi: 10.1016/j.antiviral.2015.08.011. Epub 2015 Aug 25.

Abstract

Peste des petits ruminants (PPR), caused by peste des petits ruminants virus (PPRV), is an acute or subacute, highly contagious and economically important disease of small ruminants. The PPRV is classified into the genus Morbillivirus in the family Paramyxoviridae. The PPRV matrix (M) protein possesses an intrinsic ability to bind to lipid membranes, and plays a crucial role in viral assembly and further budding. In this study, three different small interfering RNAs (siRNA) were designed on the basis of translated region for PPRV Nigeria 75/1M mRNA, and were subsequently synthesized for their transfection into Vero-SLAM cells, followed by infection with PPRVs. The results showed that two out of three siRNAs robustly induced cell-to-cell fusion as early as 36h post-infection with PPRVs, effectively suppressed expression of the M protein by interference for the M mRNA, and eventually inhibited viral replication in vitro. These findings led us to speculate that siRNA-mediated knockdown of the M protein would alter its interaction with viral glycoproteins, thus exacerbating intercellular fusion but hampering virus release.

Keywords: Cell-to-cell fusion; Inhibition; M mRNA; PPRV; Viral replication; siRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / metabolism*
  • Cell Fusion
  • Chlorocebus aethiops
  • Peste-des-petits-ruminants virus / drug effects*
  • Peste-des-petits-ruminants virus / physiology*
  • RNA, Messenger / antagonists & inhibitors*
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism*
  • Vero Cells
  • Viral Matrix Proteins / antagonists & inhibitors*
  • Viral Matrix Proteins / genetics
  • Virus Replication / drug effects*

Substances

  • Antiviral Agents
  • RNA, Messenger
  • RNA, Small Interfering
  • Viral Matrix Proteins