Nef is a protein that is produced by the HIV-1 virus that enhances the virus’s ability to infect CD41 T cells, thus contributing to immunodeficiency. A new NIAID- and NIDA-funded study by researchers at the University of Massachusetts Medical School found that Nef enhances the ability of HIV-1 to take over immune cells specifically by reducing the expression of two proteins in the surface of those cells (i.e., transmembrane proteins), SERINC3 and SERINC5. CD41 T cells lacking both of these transmembrane proteins (double-knockouts) were more than 100 times more susceptible to infection by HIV-1 viruses—even if Nef was not expressed. Together SERINC3 and SERINC5 were found to restrict HIV-1 replication, but Nef enabled the virus to evade this restriction. SERINC3 and SERINC5 are part of a larger family of proteins about which little has been known up until now, and the mechanism by which they are able to restrict viral invaders is still not understood. Another very distantly related virus, mouse leukemia virus, was also found to be able to counteract these two transmembrane proteins, suggesting that they may play a wider role in innate antiviral immunity that warrants further exploration. Finding ways to block Nef’s ability to interfere with SERINC3 and SERINC5 could represent a potential therapeutic target in fighting HIV as well as other immunodeficiency viruses.
Usami Y, Wu Y, Göttlinger HG. SERINC3 and SERINC5 restrict HIV-1 infectivity and are counteracted by Nef [published online ahead of print September 30, 2015]. Nature.