RESEARCH ARTICLE


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



Elidamar Nunes de Carvalho Lima1, 2, *, Rodrigo Sucupira Andrade Lima1, Muhammad Shoaib Arif2, José Roberto Castilho Piqueira1, Ricardo Sobhie Diaz2
1 Department of Telecommunication and Control Engineering , Engineering School, University of Sao Paulo, Sao Paulo, Brazil
2 Department of Medicine, Infectious Diseases Division, Federal University of Sao Paulo, Sao Paulo, Brazil


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Creative Commons License
© 2020 de Carvalho Lima et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Telecommunication and Control Engineering , Engineering School, University of Sao Paulo, Sao Paulo, Brazil; Tel: +55 (11) 3091-5647, +55 (11) 96326-5550; E-mail: elidamarnunes@gmail.com


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.

Keywords: Information entropy, HIV-1, C2V3C3 region, Genetic variability, Genome evolution, Immune escape.