Insights from host genomics into HIV infection and disease: Identification of host targets for drug development

Abstract

HIV susceptibility and disease progression show a substantial degree of individual heterogeneity, ranging from fast progressors to long-term non progressors or elite controllers, that is, subjects that control infection in the absence of therapy. Recent years have seen a significant increase in understanding of the host genetic determinants of susceptibility to HIV infection and disease progression, driven in large part by candidate gene studies, genome-wide association studies, genome-wide transcriptome analyses, and large-scale functional screens. These studies have identified common variants in host loci that clearly influence disease progression, characterized the scale and dynamics of gene and protein expression changes in response to infection, and provided the first comprehensive catalogue of genes and pathways involved in viral replication. This review highlights the potential of host genomic influences in antiviral therapy by pointing to promising novel drug targets but also providing the basis of the identification and validation of host mechanisms that might be susceptible targets for novel antiviral therapies.

Keywords: Genetic variation; HIV; HIV disease phenotype; Host factor; Human genomics; Novel antiviral therapy.