A pair of studies by researchers at the University of Massachusetts Medical School, the University of Trento in Italy, and the University of Geneva in Switzerland, point to a promising new anti-retroviral strategy for combating HIV-1. The two studies, published online in Nature, show that the host cell membrane proteins SERINC5 and SERINC3 greatly reduce the virulence of HIV-1 by blocking the ability of the virus to infect new cells. HIV-1 encodes a protein called Nef that counteracts the SERINCs. New drugs that target the HIV-1 protein Nef would permit the SERINC proteins to inactivate the virus. The papers will appear in the October 8 issue of Nature.
"It's amazing, the magnitude of the effect that these proteins have on infectivity," said Jeremy Luban, MD, the David J. Freelander Professor in AIDS Research and professor of molecular medicine at UMass Medical School. "The SERINC proteins reduce the infectivity of HIV-1 virions by more than 100-fold."
Heinrich Gottlinger, professor of molecular, cell and cancer biology at UMass Medical School said, "The ability of HIV to inhibit these SERINC proteins has a profound impact on its capacity to infect other cells. Disrupting this mechanism could be a very powerful strategy for treating HIV and similar viruses that express the Nef protein."
The two studies, each done independently, used completely different, yet complementary, methodologies to unravel the complex interaction between the HIV-1 protein Nef and the cell surface membrane proteins SERINC5 and SERINC3, both of which are expressed in the immune system's T cells. Dr. Luban, working with former members of his lab, Massimo Pizzato, PhD, now of the University of Trento in Italy, and Federico Santoni of the University of Geneva in Switzerland, performed massively parallel sequencing on 31 human cell lines that differed in terms of the magnitude of dependence on Nef for HIV-1 replication. Independently, Dr. Gottlinger approached the problem biochemically. Conducting proteomic analysis of purified virions, he was able to identify host cell proteins that Nef regulated.
Two studies identify promising new anti-retroviral strategy to combat HIV-1