Evidence of Divergent Amino Acid Usage in Comparative Analyses of R5- and X4-Associated HIV-1 Vpr Sequences

摘要

Vpr is an HIV-1 accessory protein that plays numerous roles during viral replication, and some of which are cell type dependent. To test the hypothesis that HIV-1 tropism extends beyond the envelope into the vpr gene, studies were performed to identify theassociations between coreceptor usage and Vpr variation in HIV-1-infected patients. Colinear HIV-1 Env-V3 and Vpr aminoacid sequences were obtained from the LANL HIV-1 sequence database and from well-suppressed patients in the Drexel/Temple Medicine CNS AIDS Research and Eradication Study (CARES) Cohort. Genotypic classification of Env-V3 sequences asX4 (CXCR4-utilizing) or R5 (CCR5-utilizing) was used to group colinear Vpr sequences. To reveal the sequences associated witha specific coreceptor usage genotype, Vpr amino acid sequences were assessed for amino acid diversity and Jensen-Shannondivergence between the two groups. Five amino acid alphabets were used to comprehensively examine the impact of amino acidsubstitutions involving side chains with similar physiochemical properties. Positions 36, 37, 41, 89, and 96 of Vpr werecharacterized by statistically significant divergence across multiple alphabets when X4 and R5 sequence groups were compared.In addition, consensus amino acid switches were found at positions 37 and 41 in comparisons of the R5 and X4 sequencepopulations. These results suggest an evolutionary link between Vpr and gp120 in HIV-1-infected patients.