HIV-1 Subtype A Gag Variability and Epitope Evolution

Abstract

ObjectiveThe aim of this study was to examine the course of time-dependent evolution of HIV-1 subtype A on a global level, especially with respect to the dynamics of immunogenic HIV gag epitopes.MethodsWe used a total of 1,893 HIV-1 subtype A gag sequences representing a timeline from 1985 through 2010, and 19 different countries in Africa, Europe and Asia. The phylogenetic relationship of subtype A gag and its epidemic dynamics was analysed through a Maximum Likelihood tree and Bayesian Skyline plot, genomic variability was measured in terms of G→A substitutions and Shannon entropy, and the time-dependent evolution of HIV subtype A gag epitopes was examined. Finally, to confirm observations on globally reported HIV subtype A sequences, we analysed the gag epitope data from our Kenyan, Pakistani, and Afghan cohorts, where both cohort-specific gene epitope variability and HLA restriction profiles of gag epitopes were examined.ResultsThe most recent common ancestor of the HIV subtype A epidemic was estimated to be 1956±1. A period of exponential growth began about 1980 and lasted for approximately 7 years, stabilized for 15 years, declined for 2–3 years, then stabilized again from about 2004. During the course of evolution, a gradual increase in genomic variability was observed that peaked in 2005–2010. We observed that the number of point mutations and novel epitopes in gag also peaked concurrently during 2005–2010.ConclusionIt appears that as the HIV subtype A epidemic spread globally, changing population immunogenetic pressures may have played a role in steering immune-evolution of this subtype in new directions. This trend is apparent in the genomic variability and epitope diversity of HIV-1 subtype A gag sequences.

Fast Dissemination of New HIV-1 CRF02/A1 Recombinants in Pakistan

“…This is significantly different from what was reported in literature and the HIV-1 sequence database [9–11]. Analysis of all available partial sequences in the database showed that only 2.6% of viral sequences were A1/G recombinant (excluding CRF02 sequences).…”

“…A number of subtypes and circulating recombinant forms (CRFs) have been reported in Pakistan [9–11], but no nationwide surveys were performed to systematically study distribution of HIV-1 subtypes and recombinants in the country. Examination of sequences available from the Los Alamos HIV Sequence Database (www.hiv.lanl.gov) showed that subtype A1 was most reported (84.3%), while subtype B, CRF02, A1/G recombinant and others accounted for 8.7%, 2.0%, 2.6% and 2.4%, respectively.…”

Prevalence of Transmitted Drug Resistance Mutations in HIV-1-Infected Drug-Naive Patients from Urban and Suburban Regions of Kenya

“…[29][30][31] To obtain an estimate of the probability of the future cooccurrence of major-minor mutations, we performed Shannon entropy analysis, which measures the probability of acquiring mutations in a given set of genomic sequences. 22 This analysis revealed that certain regions of protease gene sequences in our study cohort exhibited high entropy, indicating a higher probability of the later occurrence of mutations. The region 1-90 (HBX2 amino acids 20-50), which contained five high entropy patches (Fig.…”

“…This is consistent with previous reports on HIV subtypes in Kenya, where subtype A has been shown to be the most common HIV subtype. [20][21][22][23] The second most common viral subtype was D with a prevalence of 22%. This is also consistent with previous studies, where subtype D has been reported to be the second most prevalent subtype in Kenya (www.hiv.lanl.gov/).…”

Molecular epidemiology of HIV-1 subtype A in former Soviet Union countries

“…To examine HIV transmission networks in FSU countries, 2705 publicly available HIV-1 subtype A pol sequences were downloaded from the Los Alamos HIV Sequence Database (data available as of April 3, 2016) for thirteen countries: Armenia (2009), Azerbaijan (2001–2002), Belarus (1997–2014), Estonia (2001–2010), Georgia (1998–2003), Kazakhstan (1997–2013), Kyrgyzstan (2002–2010), Latvia (1998–2008), Lithuania (1997–2007), Moldova (1997), Russia (1986–2015), Ukraine (1996–2012), and Uzbekistan (1999–2002). These sequences were aligned, edited, and used for the construction of phylogenetic tree as described elsewhere [ 14 ] http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0093415 . Briefly, the sequences were aligned and edited using the software MEGA6 .…”