HIV-1 has a high genetic variability and can vary with respect to biological properties such as coreceptor usage, cell tropism, replication rate, sensitivity to neutralization by antibodies and cytotoxic T cells (CTL). The reverse transcriptase machinery of the virus creates mutations and mutant viruses may be selected if they have an advantage over coexisting virus variants that lack the mutation. For instance, in the presence of neutralizing antibodies, virus variants will be selected that accidentally have mutations in the neutralizing epitope, providing the virus with a neutralization resistant phenotype.
In the recent past, we have focussed on the evolution of virus variants that differed with respect to co-receptor usage. Early in infection, HIV-1 variants that only use C-C chemokine receptor 5 (CCR5; R5 variants) predominate. With progression of disease, virus variants that use C-X-C receptor 4 (CXCR4; X4 variants) emerge in about 50% of individuals.
Our current research focuses on the in-depth analysis of the molecular evolution of HIV-1 variants with different coreceptor usage, in individuals who do or do not develop X4 variants (R5X4 patients versus R5 only patients) and who are wild-type or heterozygous for a 32 base pair deletion in the CCR5 gene. In addition, we study the effect of potent humoral and cellular immunity on HIV-1 evolution and the effect mutations that allow escape from host immunity on viral replication fitness.