Elsevier

Virology

Volume 438, Issue 1, 30 March 2013, Pages 37-49
Virology

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

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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.

Highlights

► BST-2/tetherin retains CHIKV VLPs on the cell membrane. ► CHIKV structural (E1) and nonstructural proteins (nsP1) localizes with BST-2. ► BST-2 is in complex with E1 and nsP1. ► nsP1 but not E1 counteracts BST-2-mediated tethering of CHIKV VLPs. ► nsP1 but not E1 down-regulates BST-2 expression.

Abbreviations

BST-2
Bone marrow stromal cell antigen 2
CHIKV
Chikungunya virus
VLP
Virus like particle
HIV
Human immunodeficiency virus
MLV
Murine leukemia virus
MMTV
Mouse mammary tumor virus
IFNα
Interferon alpha
SEM
Scanning electron micrograph
nsPs
Nonstructural proteins
E1
Envelope glycoprotein 1
yfp
Yellow fluorescent protein

Keywords

BST-2
CHIKV
E1
Nonstructural protein
nsP1
SEM
Tetherin
VLP

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