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

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.

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.

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.

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.