Document Detail


Covariability of V3 loop amino acids.
MedLine Citation:
PMID:  8893048     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We reanalyzed for covariability a set of 308 human immunodeficiency virus type 1 (HIV-1) V3 loop amino acid sequences from the B envelope sequence subtype previously analyzed by Korber et al.,1 as well as a new set of 440 sequences that also included substantial numbers of sequences from subtypes A, D, and E. We used the measure employed by Korber et al., essentially the likelihood ratio statistic for independence, plus two additional measures as well as clade information to examine the new set and both data sets simultaneously. We set forth the following conclusions and observations. The eight most highly connected sites identified through these statistical approaches included all of the six residues previously shown to have determining roles in structure, immunologic recognition, virus phenotype, and host range; each of the seven pairs of covariant sites found by Korber were signaled by our additional two measures in the set of 308 sequences, although 2 or 3 dropped out of the examination of the set of 440 when the requirement of stringent significance was applied for some or all of the three tests, respectively; using the same criteria, a total of 20 (including 5 Korber et al. pairs) or a total of 6 (including 4 Korber et al. pairs) were found when the set of 440 was added. Several limitations to statistical analysis of this type of HIV sequence data were also noted. For example, the data sets were, by historical necessity, collected haphazardly. For example, it was not possible to separate substantially sized groups out according to time of or since infection, disease status, antiviral treatment, geography, etc. There was also an enormous "wealth of significance" within the data. For example, for one measure the 440 data set showed 233 of the 465 pairs of sites with a likelihood ratio statistic of < 0.001. Last, most sites had consensus amino acids in 80% or more of the sequences; hence, there was an absence of data on many combinations of amino acids. Given the observed linkage between sites shown to be covariable and those known to have critical biological function, the statistical approaches we and Korber et al. have outlined may find use in predicting critical structural features of HIV proteins as targets for therapeutic intervention.
Authors:
P J Bickel; P C Cosman; R A Olshen; P C Spector; A G Rodrigo; J I Mullins
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  AIDS research and human retroviruses     Volume:  12     ISSN:  0889-2229     ISO Abbreviation:  AIDS Res. Hum. Retroviruses     Publication Date:  1996 Oct 
Date Detail:
Created Date:  1997-02-10     Completed Date:  1997-02-10     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8709376     Medline TA:  AIDS Res Hum Retroviruses     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1401-11     Citation Subset:  IM; X    
Affiliation:
Department of Statistics, University of California, Berkeley 94720-3860, USA.
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MeSH Terms
Descriptor/Qualifier:
Algorithms
Amino Acid Sequence
Amino Acids / chemistry*
HIV Envelope Protein gp120 / chemistry*
Humans
Molecular Sequence Data
Peptide Fragments / chemistry*
Software
Grant Support
ID/Acronym/Agency:
AI32885-4/AI/NIAID NIH HHS; CA59039-20/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acids; 0/HIV Envelope Protein gp120; 0/HIV envelope protein gp120 (305-321); 0/Peptide Fragments

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