Evolutive Temporal Footprint of an HIV-1 Envelope Protein in an Epidemiologically Linked Cluster

Abstract

Background: The C2V3C3 region of gp 120, encoded by the HIV-1 envelope gene (env), is an important antigenic target, a key determinant for viral evolution and essential for determining epitopes for vaccines. Methods: The relationships among genetic sequence diversity, selective pressure, constraints on HIV-1 envelope protein were explored and also correlated this analysis with information entropy; hypermutation; HIV tropism; CD4+ T cell counts or HIV viral load. A total of 179 HIV-1 C2V3C3 sequences derived from cell-free plasma were used, determined from serial samples, in four epidemiologically linked individuals (one infected blood donor, two transfusion recipients and a sexual partner infected by one of the recipients) over a maximum period of 8 years. This study is important because it considers the analysis of patterns in genomic sequences, without drugs and over time. Results: A temporal relationship among information entropy, hypermutation, tropism switch, viral load, and CD4+ T cell count was determined. Changes in information entropy were time-dependent, and an increase in entropy was observed in the C2V3C3 region at amino acids G313 and F317-I320 (related to the GPGR-motif and coreceptor tropism), and at amino acids A281 in C2 and A346 in C3, related to immune escape. Conclusion: The increase of information entropy over time was correlated with hypermutation and the emergence of nonR5- strains, which are both associated with more variable genomes.