EARLY DETECTION OF SUBTYPE-SPECIFIC HIV-1 INFECTION USING TRANSCRIPTOMES FROM HOST CELL RESPONSES

Early intervention before the acute phase of HIV-1 infection is recommended to reduce viral dissemination. Here, we show the potential for host cell transcriptomes to identify sub-type specific gene signatures for HIV infection within 48 hrs of exposure to the virus. We used Affymetrix genechips to measure the effect of five distinct drug-resistant HIV-1 strains on gene expression in CD4+ MT2 T-lymphoblastoid cells. Two-way cluster analysis of 397 genes whose expression was significantly different across 6 treatment groups showed two groups of viral responses: HIV-1A17/HIV-1A17V and HIV-1RT-MDR/HIV-1HTLVIIIB/HIV-192BR019. Expression changes for TRAP100, CD83, WFS1, IRF4, GNA13, ACCN1 distinguished between the two clusters of host transcriptomes. Gene selection criteria resulted in identification of 76 genes that significantly discriminated between all 5 HIV-1 subtypes (MANOVA, p<0.0001). Leave-one-out-cross validation procedure showed 3 misclassifications (1/16 false negative, 2/16 incorrect assignments of viral group, 0/8 false positive). These results suggest that the differential changes in expression levels of 76 genes can accurately identify subtype specific HIV-1 infection of MT2 cells