Human Virus-Derived Small RNAs Can Confer Antiviral Immunity in Mammals

Immunity. 2017 Jun 20;46(6):992-1004.e5. doi: 10.1016/j.immuni.2017.05.006.


RNA interference (RNAi) functions as a potent antiviral immunity in plants and invertebrates; however, whether RNAi plays antiviral roles in mammals remains unclear. Here, using human enterovirus 71 (HEV71) as a model, we showed HEV71 3A protein as an authentic viral suppressor of RNAi during viral infection. When the 3A-mediated RNAi suppression was impaired, the mutant HEV71 readily triggered the production of abundant HEV71-derived small RNAs with canonical siRNA properties in cells and mice. These virus-derived siRNAs were produced from viral dsRNA replicative intermediates in a Dicer-dependent manner and loaded into AGO, and they were fully active in degrading cognate viral RNAs. Recombinant HEV71 deficient in 3A-mediated RNAi suppression was significantly restricted in human somatic cells and mice, whereas Dicer deficiency rescued HEV71 infection independently of type I interferon response. Thus, RNAi can function as an antiviral immunity, which is induced and suppressed by a human virus, in mammals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Argonaute Proteins / metabolism
  • Clustered Regularly Interspaced Short Palindromic Repeats
  • Enterovirus A, Human / genetics
  • Enterovirus A, Human / immunology*
  • Enterovirus Infections / immunology*
  • HEK293 Cells
  • Humans
  • Immunity*
  • Mammals
  • Mice
  • Mice, 129 Strain
  • Mice, Knockout
  • Mutation / genetics
  • RNA Interference*
  • RNA, Viral / immunology*
  • Ribonuclease III / metabolism
  • Viral Proteins / immunology


  • Argonaute Proteins
  • RNA, Viral
  • Viral Proteins
  • Ribonuclease III