Identification of novel molecular determinants of co-receptor usage in HIV-1 subtype F V3 envelope sequences

HIV-1 determinants of coreceptor usage within the gp120 V3 loop have been broadly studied over the past years. This information has led to the development of state-of the-art bioinformatic tools that are useful to predict co-receptor usage based on the V3 loop sequence mainly of subtypes B, C and A. However, these methods show a poor performance for subtype F V3 loops, which are found in an increasing number of HIV-1 strains worldwide. In the present work we investigated determinants of viral tropisms in the understudied subtype F by looking at genotypic and structural information of coreceptor:V3 loop interactions in a novel group of 40 subtype F V3 loops obtained from HIV-1 strains phenotypically characterized either as syncytium inducing or non-syncytium inducing by the MT-2 assay. We provide novel information about estimated interactions energies between a set of V3 loops with known tropism in subtype F, that allowed us to improve predictions of the coreceptor usage for this subtype. Understanding genetic and structural features underlying HIV coreceptor usage across different subtypes is relevant for the rational design of preventive and therapeutic strategies aimed at limiting the HIV-1 epidemic worldwide.