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

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.

SUBMITTER: Arantes I

PROVIDER: S-EPMC7508567 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Arantes Ighor I Ribeiro-Alves Marcelo M S D de Azevedo Suwellen S Delatorre Edson E Bello Gonzalo G

PloS one 20200922 9

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 ...[more]

PMID: 32960906

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Project description:Despite the high degree of HIV-1 protease and reverse transcriptase (RT) mutation in the setting of antiretroviral therapy, the spectrum of possible virus variants appears to be limited by patterns of amino acid covariation. We analyzed patterns of amino acid covariation in protease and RT sequences from more than 7,000 persons infected with HIV-1 subtype B viruses obtained from the Stanford HIV Drug Resistance Database (http://hivdb.stanford.edu). In addition, we examined the relationship between conditional probabilities associated with a pair of mutations and the order in which those mutations developed in viruses for which longitudinal sequence data were available. Patterns of RT covariation were dominated by the distinct clustering of Type I and Type II thymidine analog mutations and the Q151M-associated mutations. Patterns of protease covariation were dominated by the clustering of nelfinavir-associated mutations (D30N and N88D), two main groups of protease inhibitor (PI)-resistance mutations associated either with V82A or L90M, and a tight cluster of mutations associated with decreased susceptibility to amprenavir and the most recently approved PI darunavir. Different patterns of covariation were frequently observed for different mutations at the same position including the RT mutations T69D versus T69N, L74V versus L74I, V75I versus V75M, T215F versus T215Y, and K219Q/E versus K219N/R, and the protease mutations M46I versus M46L, I54V versus I54M/L, and N88D versus N88S. Sequence data from persons with correlated mutations in whom earlier sequences were available confirmed that the conditional probabilities associated with correlated mutation pairs could be used to predict the order in which the mutations were likely to have developed. Whereas accessory nucleoside RT inhibitor-resistance mutations nearly always follow primary nucleoside RT inhibitor-resistance mutations, accessory PI-resistance mutations often preceded primary PI-resistance mutations.

Project description:Functional genes of HIV-1 like the tat express proteins essential for viral survival and propagation. There are variations reported in levels of Tat transactivation among the different subtypes of HIV-1. This study looked at the amino acid differences in the different regions of Tat protein (exon 1) of subtype B and C strains of HIV-1 and tried to observe a molecular basis for protein function. HIV-1 sequences of subtype B (n=30) and C (n=60) strains were downloaded from HIV-1 Los Alamos data base. Among the 60 subtype C strain sequences, 30 each were from India and Africa. A HIV-1 Tat protein (exon 1) sequence, the consensus B and C sequence was obtained from the 'sequence search interface' in the Los Alamos HIV-1 sequence data. The sequences were visualized using Weblogo and the RNA binding regions of the three consensus sequences were also determined using BindN software program. Compared to subtype B, there was a high level of divergence in the auxiliary domain of tat exon 1 (amino acid positions 58- 69). The net charge of the subtype C (Indian) Tat protein (exon 1) auxiliary domain was -1.9 at pH 7 and it had an isoelectric point of 4.1. The net charge of the subtype C (African) auxiliary domain was -2.9 at pH 7 and it had an isoelectric point of 3.7 while the net charge of same region in subtype B was -0.9 at pH 7 with an isoelectric point of 4.9. The ratio of the hydrophilic residues to the total number of residues was 60% in the in both the Indian and African subtype C in the auxiliary domain while this was 50% in subtype B. The consensus subtype B sequence was found to have 36 RNA binding sites while subtype C (India) had 33 and subtype C (Africa) had 32 RNA binding sites. The HIV-1 Tat-TAR interaction is a potential target for inhibitors and being considered for its potential use in HIV-1 vaccines. Development of such inhibitor/vaccines would have to take into consideration the variation in amino acid sequence analyzed in this study as this could determine epitope presentation on MHC class I antigen for afferent immune response.

Dataset Information

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

Publications

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

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