报告内容摘要

HIV is a major global health problem. Despite 30 years of research, many aspects of HIV replication and pathogenesis remain mysterious, and there is no established vaccine to prevent HIV infection. Here we will describe two very different projects, one that addresses a fascinating basic aspect of HIV replication in human cells, and one that seeks to develop a preventive HIV vaccine. HIV primarily infects CD4+ T cells and macrophages in the human host. When macrophages are infected with HIV, a unique intracellular compartment forms in which viruses are sequestered. This compartment, termed the virus-containing compartment or VCC, may constitute a protected reservoir for infectious viruses. We found that VCC formation is dependent upon two cellular molecules, tetherin and Siglec-1. Tetherin is a host restriction factor that holds onto particles just after budding, while Siglec is a cell surface lectin that binds to the ganglioside GM3 on the particle membrane. Together, these molecules can capture budding virions and trigger the movement of the particles to the intracellular VCC. A different problem is posed by the quest for an effective HIV vaccine. Candidate HIV vaccines have been tested in human trials for more than 25 years, yet we do not yet have a vaccine that is proven to be protective. Our laboratory, together with the laboratory of Biao He at the University of Georgia, is pursuing a strategy that includes a live vector prime followed by boosting with HIV virus-like particles at mucosal sites. The overall goal of this approach is to generate specific immunity in the mucosa in order to prevent early infection events and subsequent disease. Our strategy employs the parainfluenza virus-type 5 (PIV-5) vector as the mucosal priming agent. We hypothesize that this unique prime-boost approach will generate cellular and humoral responses at mucosal sites that will protect against HIV infection, and we are testing this idea in an SIV/macaque challenge model.

报告人简介

Chief, Pediatric Infectious Diseases and Vice Chair for Research

Emory University Department of Pediatrics

Chief Research Officer, Children’s Healthcare of Atlanta

Atlanta, GA USA