Few amino acid signatures distinguish HIV-1 subtype B pandemic and non-pandemic strains.

Ighor Arantes,Suwellen S D De Azevedo,Marcelo Ribeiro-Alves,Edson Delatorre,Gonzalo Bello,Cecilio López-Galíndez

doi:10.1371/journal.pone.0238995

Ighor Arantes, Suwellen S D De Azevedo + Show 4 more

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https://doi.org/10.1371/journal.pone.0238995

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Abstract

The Human Immunodeficiency Virus Type I (HIV-1) subtype B comprises approximately 10% of all HIV infections in the world. The HIV-1 subtype B epidemic comprehends a pandemic variant (named BPANDEMIC) disseminated worldwide and non-pandemic variants (named BCAR) that are mostly restricted to the Caribbean. The goal of this work was the identification of amino acid signatures (AAs) characteristic to the BCAR and BPANDEMIC variants. To this end, we analyzed HIV-1 subtype B full-length (n = 486) and partial (n = 814) genomic sequences from the Americas classified within the BCAR and BPANDEMIC clades and reconstructed the sequences of their most recent common ancestors (MRCA). Analysis of contemporary HIV-1 sequences revealed 13 AAs between BCAR and BPANDEMIC variants (four on Gag, three on Pol, three on Rev, and one in Vif, Vpu, and Tat) of which only two (one on Gag and one on Pol) were traced to the MRCA. All AAs correspond to polymorphic sites located outside essential functional proteins domains, except the AAs in Tat. The absence of stringent AAs inherited from their ancestors between modern BCAR and BPANDEMIC variants support that ecological factors, rather than viral determinants, were the main driving force behind the successful spread of the BPANDEMIC strain.

Highlights

The Human Immunodeficiency Virus Type I (HIV-1) is one of the most important human pathogens that have emerged in the 20th century and exhibits an extraordinary degree of genetic variability, organized in groups (M, N, O, and P), subtypes (A-D, F-H, and J-L), subsubtypes, and many recombinant forms [1]
The maximum likelihood (ML) phylogenetic analysis of the remaining 478 subtype B FL genome American sequences revealed that most Caribbean sequences (82%) branched as basal strains and were classified as BCAR strains, while most sequences from North (97%) and South (99%) America branched in a well-supported (SH-aLRT = 0.98) monophyletic sub-clade and were classified as BPANDEMIC strains (Fig 1 and S1 Table)
We evaluate the frequency of several polymorphisms in Vif, Vpr, Nef and Rev previously associated with long-term non-progressors (LTNPs) HIV-1 infected subjects and differential protein function in vitro and ex vivo [39,40,41,42,43,44,45,46,47,48,49,50] (Table 4)

Summary

Introduction

The Human Immunodeficiency Virus Type I (HIV-1) is one of the most important human pathogens that have emerged in the 20th century and exhibits an extraordinary degree of genetic variability, organized in groups (M, N, O, and P), subtypes (A-D, F-H, and J-L), subsubtypes, and many recombinant forms [1]. HIV-1 subtype B comprises approximately 10% of all HIV infections in the world, being one of the most globally disseminated HIV-1 variants and the most prevalent subtype in the Americas, Europe, Oceania, as well as some Asian countries [2]. The HIV-1 subtype B shares a common ancestor with subtype D that was present in Kinshasa, capital of Democratic Republic of Congo (DRC), by the early 1940s [3]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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