Influence of HIV-1 Genetic Variability on Vertical Transmission and Pathogenesis
HIV-1 exists as a genetically heterogeneous population within infected individuals and in infected population. Genetic variability or viral heterogeneity plays an important role in transmission, pathogenesis, immune response, disease progression and therapy as well as is the most effective way for the virus to evade the host immune response and persists in infected individuals. We have used HIV-1 infected motherinfant pairs as a transmitter-recipient model to elucidate the role of the molecular and biological properties of HIV-1 associated with transmission and pathogenesis. HIV-1 sequences derived from infected mothers were more heterogeneous than their younger infected infants’ HIV-1 sequences. However, the infants’ HIV-1 sequences diversified as they grew older. HIV-1 infants’ sequences were different from each other but similar or closer to their mother’s sequences. We found that the minor genotypes of HIV-1 found in mothers were transmitted to their infants, which was initially maintained as a homogeneous population in infants and diversified as the infants grew older. In addition, the phenotype of these minor geno types was macrophage-tropic, nonsyncytium inducing (NSI) referred as R5 HIV-1. We also analyzed several other regions of HIV-1 genome, including env, gag p17 and NC, pol RT, tat, rev, vif, vpr, vpu and nef infected mother-infant pairs and found that there was a high functional conservation of these genes. These findings suggested that HIV-1 heterogenity plays an important role in vertical transmission and pathogenesis. The properties of transmitted viruses and those that are associated with disease progression should be targeted for the development of new strategies for prevention and treatment of HIV-1 infection. Research should focus utilizing these findings in the development of better strategies for prevention and treatment of HIV-1.