Significant changes in integrase-associated HIV-1 replication capacity between early and late isolates

During the human immunodeficiency virus type 1 (HIV-1) pandemic, continuous, extensive genetic diversification of the virus has been observed. To study the effect of HIV-1 diversification on integrase-associated viral replication capacity (RC), 94 HIV-1 subtype B integrase sequences from two groups of antiretroviral-naive viruses isolated 15 y apart were amplified and recombined with an HIV-1 infectious clone. Viral RC was determined by infecting a T cell line with a long terminal repeat-driven green fluorescent protein reporter. Significant differences in integrase-mediated RC were observed between recombinant viruses from early and late isolates (p=0.0286). Integrases from late isolates had significantly lower sequence conservation scores compared to an ancestral subtype B sequence (p<0.0001). Integrase amino acid polymorphisms S17N, I72V, S119P, and D256E were associated with a lower ex vivo viral RC. These results suggest that integrase sequence diversification has affected ex vivo HIV-1 RC.