An interferon-alpha-induced tethering mechanism inhibits HIV-1 and Ebola virus particle release but is counteracted by the HIV-1 Vpu protein.
Type 1 interferon (IFN) inhibits the release of HIV-1 virus particles via poorly defined mechanisms. Here, we show that IFNalpha induces retention of viral particles on the surface of fibroblasts, T cells, or primary lymphocytes infected with HIV-1 lacking the Vpu protein. Retained particles are tethered to cell surfaces, can be endocytosed, appear fully assembled, exhibit mature morphology, and can be detached by protease. Strikingly, expression of the HIV-1 Vpu protein attenuates the ability of human cells to adhere to, and thereby retain, nascent HIV-1 particles upon IFNalpha treatment. Vpu also counteracts the IFNalpha-induced retention of virus-like particles assembled from the Ebola virus matrix protein. Furthermore, levels of IFNalpha that suppress replication of Vpu-defective HIV-1 have little effect on wild-type HIV-1. Thus, we propose that HIV-1 expresses Vpu to counteract an IFNalpha-induced, general host defense that inhibits dissemination of enveloped virions from the surface of infected cells.
Neil
Stuart J D
SJ
Aaron Diamond AIDS Research Center and the Laboratory of Retrovirology, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
Sandrin
Virginie
V
Sundquist
Wesley I
WI
Bieniasz
Paul D
PD
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D029043:Ebolavirus / Q000254:growth & development* / Q000276:immunology; D015497:HIV-1 / Q000254:growth & development* / Q000276:immunology; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology*; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000502:physiology*; D014771:Virion / Q000276:immunology; D000086082:Viroporin Proteins
D054298:Human Immunodeficiency Virus Proteins; D016898:Interferon-alpha; D054334:Viral Regulatory and Accessory Proteins; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins