This is project to continue the study of host genetic resistance to HIV-1. The project evolved from early studies which showed that CD4 lymphocytes from random individuals possessed differential susceptibility to certain strains of T cell- trophic HIV. This appeared to be genetically determined because the susceptible or resistant phenotype was consistent for a given donor and a given HIV strain, and because it segregated in a family. Two years of work have demonstrated further that this differential susceptibility is genetically determined as judged by more family segregation studies, and that it appears to be a unique resistance which is a post-entry restriction of the virus and is not receptor-mediated. Other studies during this period have shown, also, that two cases of """"""""transient"""""""" HIV infection in adults are associated with this host lymphocyte resistance. Two new cohorts of high-risk individuals have been established and are currently under study to determine the frequency of transient infection and if host genetic resistance to T cell-trophic HIV strains is playing a role in both transient infection and in resistance to infection.
The specific aims of the project: (1) to map the viral determinant of this host resistance; (2) to map the resistance genes in the human genome; and (3) to demonstrate further whether these genes have a role in the human population in either preventing infection or retarding disease progression. In effect, the researchers in this project will characterize a third type of genetic resistance to HIV, adding to the HLA/TAP complex and the chemokine receptor polymorphisms.
| Sahu, G K; Chen, J J; Huang, J C et al. (2001) Transient or occult HIV-1 infection in high-risk adults. AIDS 15:1175-7 |
| Wang, L; Chen, J J; Gelman, B B et al. (1999) A novel mechanism of CD4 lymphocyte depletion involves effects of HIV on resting lymphocytes: induction of lymph node homing and apoptosis upon secondary signaling through homing receptors. J Immunol 162:268-76 |
| Wentz, M P; Moore, B E; Cloyd, M W et al. (1997) A naturally arising mutation of a potential silencer of exon splicing in human immunodeficiency virus type 1 induces dominant aberrant splicing and arrests virus production. J Virol 71:8542-51 |
| Wang, L; Robb, C W; Cloyd, M W (1997) HIV induces homing of resting T lymphocytes to lymph nodes. Virology 228:141-52 |
