MicrobiologyBytes

If you’ve studied virology, you’ll be familiar with the concept of a virus attachment protein, the protein(s) a virus uses to bind to the receptors on a host cell during infection. That’s all very well, but what happens after the virus has replicated and the new particles want to leave to find new host cells? How do they avoid getting stuck on the cell surface like flies on fly-paper? Mammals have evolved various mechanisms to foil the spread of viruses. One such restriction factor prevents HIV-1 from leaving infected cells and is counteracted by an HIV protein called Vpu. Without its Vpu protein, the HIV-1 gets stuck to the surface of the human cell in which it has replicated. The mysterious factor that tethers HIV-1 to the host cell is probably a cell-membrane protein.

Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 451, 425-430
Human cells possess an antiviral activity that inhibits the release of retrovirus particles, and other enveloped virus particles, and is antagonized by the HIV-1 accessory protein, Vpu. This antiviral activity can be constitutively expressed or induced by interferon-alpha, and it consists of protein-based tethers, which we term ‘tetherins’, that cause retention of fully formed virions on infected cell surfaces. Using deductive constraints and gene expression analyses, we identify CD317, a membrane protein of previously unknown function, as a tetherin. Specifically, CD317 expression correlated with, and induced, a requirement for Vpu during HIV-1 and murine leukaemia virus particle release. Furthermore, in cells where HIV-1 virion release requires Vpu expression, depletion of CD317 abolished this requirement. CD317 caused retention of virions on cell surfaces and, after endocytosis, in CD317-positive compartments. Vpu co-localized with CD317 and inhibited these effects. Inhibition of Vpu function and consequent mobilization of tetherin’s antiviral activity is a potential therapeutic strategy in HIV/AIDS.

Related:

• Chemokines, receptors and virus infection
• Variation in two key genes can predict the course of progression to AIDS
• The Interferon Antiviral Response

Tags: Biology, Health, HIV/AIDS, Medicine, Microbiology, Science, Virology

This entry was posted on Thursday, February 14th, 2008 at 3:43 am and is filed under Biology, Health, HIV/AIDS, Medicine, Microbiology, Science, Virology. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed.