Human immunodeficiency virus reverse transcriptase and protease sequence database.

Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
Nucleic Acids Research (Impact Factor: 8.81). 02/2003; 31(1):298-303.
Source: PubMed

ABSTRACT The HIV reverse transcriptase and protease sequence database is an on-line relational database that catalogues evolutionary and drug-related sequence variation in the human immunodeficiency virus (HIV) reverse transcriptase (RT) and protease enzymes, the molecular targets of antiretroviral therapy ( The database contains a compilation of nearly all published HIV RT and protease sequences, including submissions to GenBank, sequences published in journal articles and sequences of HIV isolates from persons participating in clinical trials. Sequences are linked to data about the source of the sequence, the antiretroviral drug treatment history of the person from whom the sequence was obtained and the results of in vitro drug susceptibility testing. Sequence data on two new molecular targets of HIV drug therapy--gp41 (cell fusion) and integrase--will be added to the database in 2003.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The effects on virus viability and reverse transcriptase (RT) function of substituting Trp for Tyr or Phe residues within the polymerase domain of human immunodeficiency virus type 1 (HIV-1) RT have been analyzed with an infectious HIV-1 clone. Viruses containing mutations Y56W, F61W, F87W, F116W, Y127W, Y144W, F171W, Y181W, Y183W, Y188W, F227W, or Y232W in their RT-coding regions were viable and showed replication capacities similar or slightly reduced in comparison with the wild-type HIV-1. However, RTs bearing mutations F77W or Y146W had a dNTP-binding defect, rendering nonviable viruses. HIV-1 carrying RT mutations F124W or F130W replicated very poorly, but compensatory changes (K83R for F124W, and T58S for F130W) were selected upon passaging the virus in cell culture. The amino acid substitution F130W diminishes the stability of the 51-kDa subunit of the RT (p51) and impairs polyprotein processing in virus-infected cells, an effect that can be mitigated when T58S is found in p51.
    Virology 05/2004; DOI:10.1016/S0042-6822(04)00257-0 · 3.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background South Africa has a generalized and explosive HIV/AIDS epidemic with the largest number of people infected with HIV-1 in the world. Molecular investigations of HIV-1 diversity can help enhance interventions to contain and combat the HIV/AIDS epidemic. However, many studies of HIV-1 diversity in South Africa tend to be limited to the major metropolitan centers and their surrounding provinces. Hardly any studies of HIV diversity have been undertaken in Mpumalanga Province, and this study sought to investigate the HIV-1 diversity in this province, as well as establish the occurrence and extent of transmitted antiretroviral drug resistance mutations. Methods HIV-1 gag p24, pol p10 and p66/p51, pol p31 and env gp41 gene fragments from 43 participants were amplified and sequenced. Quality control on the sequences was carried out using the LANL QC online tool. HIV-1 subtype was preliminary assigned using the REGA 3.0 and jpHMM online tools. Subtype for the pol gene fragment was further designated using the SCUEAL online tool. Phylogenetic analysis was inferred using the Maximum Likelihood methods in MEGA version 6. HIV-1 antiretroviral drug resistance mutations were determined using the Stanford database. Results Phylogenetic analysis using Maximum Likelihood methods indicated that all sequences in the study clustered with HIV-1 subtype C. The exception was one putative subtype BC unique recombinant form. Antiretroviral drug resistance mutations K103N and E138A were also detected, indicating possible transmission of anti-retroviral drug resistance mutations. Conclusions The phylogenetic analysis of the HIV sequences revealed that, by 2009, patients in the Bushbuckridge, Mpumalanga were predominantly infected with HIV-1 subtype C. However, the generalized, explosive nature of the HIV/AIDS epidemic in South Africa, in the context of extensive mobility by South Africans who inhabit rural areas, renders the continued molecular monitoring and surveillance of the epidemic imperative. Electronic supplementary material The online version of this article (doi:10.1186/s12985-015-0244-1) contains supplementary material, which is available to authorized users.
    Virology Journal 02/2015; 12(1). DOI:10.1186/s12985-015-0244-1 · 2.09 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background In this study, clustering was performed using a bitmap representation of HIV reverse transcriptase and protease sequences, to produce an unsupervised classification of HIV sequences. The classification will aid our understanding of the interactions between mutations and drug resistance. 10,229 HIV genomic sequences from the protease and reverse transcriptase regions of the pol gene and antiretroviral resistant related mutations represented in an 82-dimensional binary vector space were analyzed.ResultsA new cluster representation was proposed using an image inspired by microarray data, such that the rows in the image represented the protein sequences from the genotype data and the columns represented presence or absence of mutations in each protein position.The visualization of the clusters showed that some mutations frequently occur together and are probably related to an epistatic phenomenon.Conclusion We described a methodology based on the application of a pattern recognition algorithm using binary data to suggest clusters of mutations that can easily be discriminated by cluster viewing schemes.
    BMC Bioinformatics 02/2015; 16(1):35. DOI:10.1186/s12859-015-0452-0 · 2.67 Impact Factor


Available from