Genomic Utility for Association and Viral Analyses in HIV

HIV-1 susceptibility is partially dependent on host genetics. In this GWAS of resistance against HIV-1 infection 431 hemophilia patients highly exposed to potentially contaminated factor VIII transfusions were compared to 765 HIV-infected controls.

HIV-1 viral load at set point is a strong correlate of disease progression. GWAS and exome sequencing were performed in carefully selected subsets of the Swiss HIV Cohort Study (http://www.shcs.ch).

A small number of people demonstrate sustained ability to control HIV replication at low levels without therapy. These HIV controllers maintain stable CD4+ T cell counts, do not develop clinical disease, and are less likely to transmit HIV to others. A GWAS was performed comparing 516 HIV controllers to 1196 individuals with progressive infection as part of the International HIV Controllers Study.

Selection pressures arising from host genomic factors affect HIV-1 sequence diversity. Amino acid variants of HIV-1 were used as phenotypes in 1071 individuals with paired host/viral genetic data. This strategy allowed a global assessment of host-pathogen interactions at the genome level and revealed sites of genomic conflict between the HLA region and the HIV-1 proteome.

Every individual harbors ~20,000 unique coding variants, including potentially severe premature stop codons or frameshifts. Publicly available data from the <a href="http://evs.gs.washington.edu/EVS">NHLBI Exome Sequencing Project</a> provides a population level survey of genetic variants within genes in >6000 individuals of European ancestry and >2000 African Americans. This detailed level of protein sequence variation information allows for visualization and first-pass estimation of the level of conservation or variation of a given gene.

Transcriptome analysis are revealing of the biological process during HIV infection. Gene expression in CD4+ T cells isolated from HIV-infected individuals representing the full spectrum of disease and viral load were investigated (CD4_Expression). In vitro analysis captured the dynamic process of the viral cycle in a permissive cell line (SupT1) over 24 hours (Viral_Cycle), and the process of latency and reactivation upon pharmacological or immunological stimuli in a primary CD4+ T cell model (Latency).

Every individual harbors ~20,000 unique coding variants, including potentially severe premature stop codons or frameshifts. These data represents exome sequencing results from HIV-infected population. This detailed level of protein sequence variation information allows for visualization and first-pass estimation of functional variants of interest for HIV biology.