Infectious Lassa virus, but not filoviruses, is restricted by BST-2/tetherin

Sheli R. Radoshitzky, Lian Dong, Xiaoli Chi, Jeremiah C. Clester, Cary Retterer, Kevin Spurgers, Jens H. Kuhn, Sarah Sandwick, Gordon Ruthel, Krishna Kota, Dutch Boltz, Travis Warren, Philip J. Kranzusch, Sean P.J. Whelan, Sina Bavari

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

Bone marrow stromal antigen 2 (BST-2/tetherin) is a cellular membrane protein that inhibits the release of HIV-1. We show for the first time, using infectious viruses, that BST-2 also inhibits egress of arenaviruses but has no effect on filovirus replication and spread. Specifically, infectious Lassa virus (LASV) release signifi-cantly decreased or increased in human cells in which BST-2 was either stably expressed or knocked down, respectively. In contrast, replication and spread of infectious Zaire ebolavirus (ZEBOV) and Lake Victoria marburgvirus (MARV) were not affected by these conditions. Replication of infectious Rift Valley fever virus (RVFV) and cowpox virus (CPXV) was also not affected by BST-2 expression. Elevated cellular levels of human or murine BST-2 inhibited the release of virus-like particles (VLPs) consisting of the matrix proteins of multiple highly virulent NIAID Priority Pathogens, including arenaviruses (LASV and Machupo virus [MACV]), filoviruses (ZEBOV and MARV), and paramyxoviruses (Nipah virus). Although the glycoproteins of filoviruses counteracted the antiviral activity of BST-2 in the context of VLPs, they could not rescue arenaviral (LASV and MACV) VLP release upon BST-2 overexpression. Furthermore, we did not observe colocalization of filoviral glycoproteins with BST-2 during infection with authentic viruses. None of the arenavirus-encoded proteins rescued budding of VLPs in the presence of BST-2. Our results demonstrate that BST-2 might be a broad antiviral factor with the ability to restrict release of a wide variety of human pathogens. However, at least filoviruses, RVFV, and CPXV are immune to its inhibitory effect.

Original languageEnglish
Pages (from-to)10569-10580
Number of pages12
JournalJournal of virology
Volume84
Issue number20
DOIs
StatePublished - Oct 1 2010
Externally publishedYes

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    Radoshitzky, S. R., Dong, L., Chi, X., Clester, J. C., Retterer, C., Spurgers, K., Kuhn, J. H., Sandwick, S., Ruthel, G., Kota, K., Boltz, D., Warren, T., Kranzusch, P. J., Whelan, S. P. J., & Bavari, S. (2010). Infectious Lassa virus, but not filoviruses, is restricted by BST-2/tetherin. Journal of virology, 84(20), 10569-10580. https://doi.org/10.1128/JVI.00103-10