Suppression of production of baboon endogenous virus by dominant negative mutants of cellular factors involved in multivesicular body sorting pathway

Virus Res. 2015 Jan 22:196:128-34. doi: 10.1016/j.virusres.2014.11.020. Epub 2014 Nov 22.

Abstract

Baboon endogenous virus (BaEV) is an infectious endogenous gammaretrovirus isolated from a baboon placenta. BaEV-related sequences have been identified in both Old World monkeys and African apes, but not in humans or Asian apes. Recently, it was reported that BaEV-like particles were produced from Vero cells derived from African green monkeys by chemical induction, and thus BaEV-like particles may contaminate biological products manufactured using Vero cells. In this study, we constructed an infectious molecular clone of BaEV strain M7. We found two putative L-domain motifs, PPPY and PSAP, in the pp15 region of Gag. To examine the function of the L-domain motifs, we conducted virus budding assay using L-domain motif mutants. We revealed that the PPPY motif, but not the PSAP motif, plays a major role as the L-domain in BaEV budding. We also demonstrated that Vps4A/B are involved in BaEV budding. These data suggest that BaEV Gag recruits the cellular endosomal sorting complex required for transport (ESCRT) machinery through the interaction of the PPPY L-domain with cellular factors. These data will be useful for controlling contamination of BaEV-like particles in biological products in the future.

Keywords: Baboon; Baboon endogenous virus; Budding; Host factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Chlorocebus aethiops
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Gammaretrovirus / physiology*
  • Gene Products, gag / chemistry
  • Gene Products, gag / genetics
  • Genome, Viral
  • Host-Pathogen Interactions
  • Humans
  • Molecular Sequence Data
  • Multivesicular Bodies / metabolism*
  • Multivesicular Bodies / virology
  • Mutation*
  • Protein Interaction Domains and Motifs
  • RNA, Viral
  • Vero Cells
  • Virus Release
  • Virus Replication*

Substances

  • Endosomal Sorting Complexes Required for Transport
  • Gene Products, gag
  • RNA, Viral