DC-SIGN/R Polymorphisms and HIV-1 Infection in China

University Of Washington, Seattle WA

Investigators

Linked publications & trials

Abstract

[unreadable] DESCRIPTION (provided by applicant): This supplement, in response to the CFAR RFA Area 1, proposes a collaboration of the University of Washington CFAR at an important international site in Guangdong, China, which is currently experiencing one of the most rapidly expanding HIV epidemics in the world. The proposed training and research will revolve around the establishment of HlV-seronegative high-risk and HIV-1 infected cohorts that will prospectively be followed at collaborative sites. Research will focus on studies of polymorphisms of dendritic cell (DC)-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and the DC-SIGN homologue (DC-SIGNR), [unreadable] and their protective role in infection with HIV-1 subtypes B', C and E. We demonstrated that DC-SIGN and DC-SIGNR heterozygosity correlates with resistance to HIV-1 infection in Caucasians in the U.S., where subtype B dominates. However, we could not determine the association of these polymorphisms with HIV-1 subtype B or other subtypes in non-Caucasian ethnic populations. In the present application, we will initiate a project in Asia with the Jinan University (JU) in Guangdong to pursue a global study to determine the influence of the DC-SIGN and DC-SIGNR polymorphisms on infection, particularly with different HIV-1 subtypes in multiple ethnicities and geographical regions. To support this research goal, we will provide training that is directly relevant to the research project proposed, to establish study cohorts and build research capacity in Guangdong. The scientific aims are: (1) To determine the [unreadable] general frequency and distribution of DC-SIGN and DC-SIGNR polymorphisms among Chinese populations where HIV-1 subtypes B', C and E are co-circulating, to determine if the polymorphisms have an influence on the epidemiology of the HIV-1 pandemic with different HIV-1 subtypes in China, and (2) To determine the distribution of DC-SIGN and DC-SIGNR polymorphisms in specific cohorts of exposed seronegatives (ES), HIV-1 seropositives and seronegatives to evaluate their effect on HIV-1 infection in Chinese populations. We will determine if and/or how each polymorphism influences infection with HIV-1 subtypes B', C and E. These studies complement and integrate into our international study on the DC-SIGN and DC-SIGNR polymorphisms in Northern America, Southern America and Africa through collaborations with UW CFAR faculty. The research capacity, infrastructure and cohorts of high-risk HIV-1 seronegatives and HIV-1 positives to be established will provide a foundation for future collaborative studies searching for new anti-HIV gene variants, as well as clinical trials of HIV prevention, treatment and vaccine. [unreadable] [unreadable]