Tetherin (ST2/CD317) is a cellular protein that restricts the release from cells of some enveloped viruses including HIV-1. To examine if influenza virus is affected by tetherin, MDCK cells constitutively expressing human tetherin and control MDCK cells were infected with influenza virus. No difference was observed in infectious titers, at 24 h or 48 h post-infection. In contrast, tetherin expression inhibited influenza virus-like particle (VLP) release into the media. Expression of the HIV protein Vpu overcame the tetherin block of influenza virus VLPs. A human tetherin mutant that lacks a C-terminal GPI anchor attachment signal (tetherin-ΔGPI) was constructed to test if this mutant could be incorporated into the released virus or VLP particles. Whereas tetherin-ΔGPI was incorporated into influenza VLPs it was not incorporated into influenza virions. Taken together these data suggest that influenza virions may contain a tetherin antagonist.
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