BST-2/tetherin-mediated restriction of chikungunya (CHIKV) VLP budding is counteracted by CHIKV non-structural protein 1 (nsP1)

Virology. 2013 Mar 30;438(1):37-49. doi: 10.1016/j.virol.2013.01.010. Epub 2013 Feb 12.

Abstract

Chikungunya virus (CHIKV) is a re-emerging alphavirus transmitted by Aedes mosquitoes. Infection with CHIKV elicits a type I interferon response that facilities virus clearance, probably through the action of down-stream effectors such as antiviral IFN-stimulated genes (ISGs). Bone marrow stromal antigen 2 (BST-2) is an ISG shown to restrict HIV-1 replication by preventing the infection of bystander cells by tethering progeny virions on the surface of infected cells. Here we show that enrichment of cell surface BST-2 results in retention of CHIKV virus like particles (VLPs) on the cell membrane. BST-2 was found to co-localize with CHIKV structural protein E1 in the context of VLPs without any noticeable effect on BST-2 level. However, CHIKV nonstructural protein 1 (nsP1) overcomes BST-2-mediated VLPs tethering by down-regulating BST-2 expression. We conclude that BST-2 tethers CHIKV VLPs on the host cell plasma membrane and identify CHIKV nsP1 as a novel BST-2 antagonist.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism*
  • Cell Line
  • Chikungunya virus / immunology*
  • Chikungunya virus / pathogenicity*
  • Chikungunya virus / physiology
  • GPI-Linked Proteins / antagonists & inhibitors
  • GPI-Linked Proteins / metabolism
  • Host-Pathogen Interactions*
  • Humans
  • Viral Nonstructural Proteins / metabolism*
  • Virus Release*

Substances

  • Antigens, CD
  • BST2 protein, human
  • GPI-Linked Proteins
  • Viral Nonstructural Proteins