Title: INTERFERON RESISTANCE IN THE TRANSMITTED HIV-1 ENVELOPE GLYCOPROTEIN
(hiv-1包膜糖蛋白的干扰素耐药性)
Stuart Neil, King’s College London
Abstract
Resistance to type-1 interferons (IFN-I) is essential for the transmission fitness of HIV-1. Whilst transmitted viruses are derived from the most IFN-resistant sequences found in the semen of transmitting partners, this IFN-I resistance wanes over the course of acute and chronic infection. Although the determinants of this are multiple, we have recently found that intrinsic IFN-resistance in the envelope glycoprotein is a major contributor. IFN-I induces the expression of a variety of proteins with direct antiviral activity, of which the Interferon Induced Transmembrane (IFITMs) directly inhibit the cellular entry of diverse enveloped viruses. We have found that most HIV-1 isolates are variably sensitive to IFITM-mediated restriction, depending on its receptor/co-receptor usage and the subcellular localization of the IFITM itself, implying that different viral isolates enter the cell at distinct sites. In contrast, the envelope glycoproteins of transmitted viruses are completely resistant to IFITM-mediated restriction. After 6 months of infection, however, circulating viruses from the same individual have developed significant sensitivities to one or more human IFITMs. This is determined by adaptations in envelope that allow escape from autologous neutralizing antibody responses. The gain in IFITM restriction contributes significantly to these virus’ increased IFN-I sensitivity in primary CD4+ T cells. Thus these data imply a structural constraint on the envelope at transmission that confers IFITM and IFN resistance. I will discuss these data and some recent unpublished observations that follow from them
Biosketch
Stuart Neil is currently Professor of Virology in the Department of Infectious Disease at King’s College London, where he set up his independent research group in 2008. After receiving his PhD in 2001 from University College London, Prof Neil worked as a postdoctoral researcher in the groups of Robin Weiss (UCL) and later that of Paul Bieniasz at Aaron Diamond AIDS Research Center in New York. It was here that he discovered that the antiviral protein Tetherin (or BST-2) restricted HIV-1 particle release and was counteracted by the accessory protein Vpu. In the ensuing time, Prof Neil’s group has worked extensively on the restriction of lentiviruses by Tetherin and the biology of Vpu. This research has broadened out into understanding the role of other plasma membrane-based restrictions in HIV-1 pathogenesis, as well as a wide ranging research interest in the basic biology and host restriction of Ebola virus replication.
Time: Oct. 3th, 2017, 13:30-15:15
Venue: Medical Science Building, Room B323
Host: Prof. Xu Tan
举办单位：生命科学联合中心
