Scientists Elucidate How an HIV Protein Neutralizes an Inhibiting Host Factor
Process could also explain pandemic spread of the disease, as reported in PLoS Pathogens.!--h2>
Investigators at the Institut de recherches cliniques de Montreal (IRCM) have figured out how the Vpu viral protein prevents expression of Tetherin, a host factor that inhibits HIV-1 release, on the surface of infected cells. Furthermore, they suggest that HIV-1’s development of this mechanism could have contributed to the pandemic spread of the disease.
Findings are published in PLoS Pathogens in a paper titled “Antagonism of Tetherin Restriction of HIV-1 Release by Vpu Involves Binding and Sequestration of the Restriction Factor in a Perinuclear Compartment.”
“Tetherin is a cellular protein that captures viruses forming at the surface of infected cells, thereby preventing viral transmission and spread,” explains Dr. Éric A Cohen, director of the human retrovirology research unit at IRCM. “This antiviral protein, whose production is triggered by interferon, is an effector of the innate immune response against viral infections.
“However, viruses, and especially HIV-1, have evolved and developed mechanisms that antagonize this restriction factor. In fact, we have discovered how the Vpu protein neutralizes Tetherin and as such stimulates HIV-1 production.”
By directly binding Tetherin, Vpu adversely affects the transport of the restriction factor to the cell surface, which is the site of its antiviral activity. Tetherin is therefore stored within the cell, thus preventing it from playing its role as a barrier against virus transmission.
“Simian immunodeficiency viruses, considered to be precursors of HIV-1, are unable to antagonize human Tetherin,” points out Mathieu Dub, doctorate candidate at the IRCM's human retrovirology research unit and first author of the article. “It would appear that the emergence of HIV-1 strains encoding Vpu proteins with the ability to perturb the intracellular transport of human Tetherin could have contributed to the pandemic spread of certain groups of HIV-1.”