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.
Highlights
The ability of HIV-1 to rapidly evolve is one of its most striking features, enabling its immune escape and favoring its persistence in an infected host [1, 2]
HIGHLIGHTS √ Increased information entropy correlates with a tropism switch from R5 to non-R5 strains
A correlation between information entropy and viral load was observed in all individuals but was statistically significant only in D.O.(p
Summary
The ability of HIV-1 to rapidly evolve is one of its most striking features, enabling its immune escape and favoring its persistence in an infected host [1, 2]. The HIV-1 envelope gene (env) encodes the viral envelope glycoprotein, which is a heavily glycosylated trimer of non-covalently linked, heterodimeric glycoproteins composed of the surface-exposed gp120 and the transmembrane gp. Extensive N-linked glycosylation of the envelope glycoprotein effectively shields many of its conserved epitopes from antibody recognition. Gp120 is divided into five conserved regions (C1-C5) and five hypervariable loops (V1-V5). Acids long, frequently glycosylated, and highly variable and has a disulfide-bonded structure that has potential impact on several functions of the envelope protein. The V3 loop harbors the most important determinants of viral tropism (i.e., coreceptor usage), as well as major antigenic neutralizing epitopes [3 - 6]. 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
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