Human Genes and Related Polymorphysims that Affect HIV Infection and Disease Progression

CFAR Clinical Research Pilot Project, Tuofu, Zhu, MD

Extensive studies indicate that host genetic variability affects the risk for HIV-1 infection and disease progression.   This variability comes from polymorphisms in genes such as C-C chemokine receptor 5 (CCR5)-Δ32, CCR5 promoter polymorphisms, CCR2-64I, SDF1-3'A, and RANTES -28G / -403A.   Among these, only CCR5-Δ32 has clearly shown to be associated with the resistance to HIV-1 infection.   We have screened our cohorts of Exposed Seronegative (ES) , HIV-1 infected, HIV-1 negative, and long term non-progressors for these polymorphisms as well as the coding regions of CCR5, CXCR4, CCR1, CCR2b, CCR3 and CCR4. As reported by other groups, we observed that only homozygous CCR5-Δ32 is convincingly associated with the ressistance to HIV-1 infection in our ES.   However, homozygous CCR5-Δ32 is found only in 3% (2/60) in our ES (same in other reported Caucasian ES cohorts) and 1% of general Caucasian population, but not in Africans and Asians. These results indicate other human genetic mutations that may affect HIV-1 infection.

In the past years, we have screened for new host gene polymorphisms that may affect HIV transmission and/or diseases progression. We have identified new genetic polymorphisms that affect HIV-1 transmission. We plan to extend these studies by: (1) conducting further study in larger populations worldwide; (2) searching for new human genes; (3) conducting function studies on newly identified mutants and develop theraputic stategies for HIV-1 infection.