In two separate papers, Massimo Pizzato and colleagues and Heinrich Göttlinger and colleagues identify previously unrecognized restriction factors for HIV-1. In the absence of the HIV-1 Nef protein, the multipass transmembrane proteins SERINC3 and SERINC5 become incorporated into assembling virions and profoundly block HIV-1 infection. The Nef protein, which is normally expressed by HIV-1, counteracts this activity by down-regulating SERINC3 and SERINC5 from the cell surface, thereby preventing their incorporation into virions. These findings identify SERINC5, and to a lesser extent SERINC3, as the agents responsible for the long-sought anti-HIV-1 activity that is overcome by Nef. This raises the possibility that SERINC5 might have potential as a basis for anti-HIV-1 therapeutics.
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