Poxvirus superinfection is halted at the stage of virus-cell membrane fusion independently of primary virus gene expression

Tuesday, October 09, 2012 — Poster Session I
1:00 p.m. – 3:00 p.m	Natcher Conference Center, Building 45	NIAID	VIROL-9

* FARE Award Winner

Authors

• J.P. Laliberte
• B. Moss

Abstract

Vaccinia virus (VACV) – the prototypic poxvirus – encodes ~200 proteins within its 195-kbp dsDNA genome. Poxviruses replicate exclusively in the cytoplasm upon infection and display rapid spread in tissue culture. Poxvirus entry into already infected cells – superinfection – is potently blocked by the viral A56 and K2 proteins. Here we describe an additional superinfection exclusion mechanism that is independent of viral gene expression. Inhibition of superinfecting virus occurred at the virus-cell membrane fusion step of entry and exclusion was dependent on multiplicity and duration of the primary infection. Attachment of primary virus was required but not sufficient to inhibit superinfection as entry-impaired virions allowed superinfection. Furthermore, primary virus transcription alone triggered exclusion of superinfecting virus. Cells infected with ΔA56/ΔK2 virus, however, were equally non-permissive to superinfection compared to wildtype controls and secondary virus was also halted at virus-cell fusion. Our results indicate the existence of alternative and redundant mechanisms to prevent superinfection. We suggest that cellular membrane changes triggered by the primary infection render the cell incompetent to mediate a subsequent poxvirus infection. Given the promising use of poxviruses as vaccine and gene therapy vectors, the further study and elucidation of such poxvirus-host cell interactions are warranted.

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