Zinc finger antiviral protein (ZAP) inhibits small ruminant morbillivirus replication in vitro

Vet Microbiol. 2021 Sep:260:109163. doi: 10.1016/j.vetmic.2021.109163. Epub 2021 Jun 23.

Abstract

Small ruminant morbillivirus (SRMV) is a highly contagious and economically important viral disease of small domestic and wild ruminants. Difficulty with its stable proliferation in ovis aries-derived cells has led to a relative lag in the study of its natural immunity and pathogenesis. Here we report the antiviral properties of ZAP against SRMV, a single-stranded negative-stranded RNA virus of the genus Morbillivirus. ZAP expression was significantly induced in sheep endometrial epithelial cells following SRMV infection. ZAP inhibited SRMV replication in cells after infection, while its overexpression in Vero-SLAM cells significantly increased their resistance to SRMV replication. The ZAP protein co-localized with SRMV RNA in the cytoplasm and ZAP-responsive elements were mapped to the 5' untranslated region of SRMV nucleocapsid, phosphoprotein, matrix, and fusion. In summary, ZAP confers resistance to SRMV infection by directly targeting viral RNA and inhibiting viral replication. Our findings further extend the ranges of viral targets of ZAP and help elucidate the mechanism of SRMV replication.

Keywords: Replication; Small ruminant morbillivirus (SRMV); ZRE; Zinc finger antiviral protein (ZAP).

MeSH terms

  • Animals
  • Chlorocebus aethiops
  • Endometrium / virology
  • Epithelial Cells / virology
  • Female
  • HEK293 Cells
  • Humans
  • Morbillivirus / physiology*
  • Morbillivirus Infections / veterinary*
  • Morbillivirus Infections / virology
  • RNA, Viral / genetics
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Sheep
  • Vero Cells
  • Virus Replication

Substances

  • RNA, Viral
  • RNA-Binding Proteins
  • ZC3HAV1 protein, human