Abstract
The interferon-induced host cell factor tetherin inhibits release of human immunodeficiency virus (HIV) from the plasma membrane of infected cells and is counteracted by the HIV-1 protein Vpu. Influenza A virus (FLUAV) also buds from the plasma membrane and is not inhibited by tetherin. Here, we investigated if FLUAV encodes a functional equivalent of Vpu for tetherin antagonism. We found that expression of the FLUAV protein NS1, which antagonizes the interferon (IFN) response, did not block the tetherin-mediated restriction of HIV release, which was rescued by Vpu. Similarly, tetherin-mediated inhibition of HIV release was not rescued by FLUAV infection. In contrast, FLUAV infection induced tetherin expression on target cells in an IFN-dependent manner. These results suggest that FLUAV escapes the antiviral effects of tetherin without encoding a tetherin antagonist with Vpu-like activity.
Highlights
The interferon (IFN) system is an integral part of the innate defenses against viral infection [1]
These results indicate that FLUAV release is not efficiently inhibited by tetherin, in accordance with published work [22,24], a modest blockade of FLUAV release can be observed upon engineered expression of high levels of tetherin
Several enveloped viruses which are targeted by tetherin encode for tetherin antagonists, which allow for efficient viral spread in tetherin expressing target cells [26,27]
Summary
The interferon (IFN) system is an integral part of the innate defenses against viral infection [1]. While important sensors and signal transducers of the IFN system have been identified, the nature of the ISGs responsible for the transition of cells into an antiviral state is less well defined. Tetherin is a recently identified IFN-induced host cell protein, which was initially shown to restrict release of human immunodeficiency virus type 1 (HIV-1) particles from infected cells and to be counteracted by the HIV-1 protein Vpu [2,3]. The presence of two membrane anchors in tetherin, an N-terminal transmembrane domain and a C-terminal GPI anchor, is critical for tetherin’s antiviral activity, since they allow tetherin to simultaneously insert into the viral and the cellular membrane, thereby forming a tether between virion and host cell [13]
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