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Epitopes that are presented to CTLs are first processed in the presenting cell in several steps, including proteasomal cleavage, transport to the endoplasmic reticulum, binding by the HLA molecule, and finally presentation to the T-cell receptor. An understanding of the potential of the virus to escape CTL responses can aid in designing an effective vaccine. To investigate such a potential, we analyzed HIV-1<jats:italic>gag<\/jats:italic>from 468 HIV-1-positive Kenyan women by using several bioinformatic approaches that allowed the identification of positively selected amino acids in the HIV-1<jats:italic>gag<\/jats:italic>region and study of the effects that these mutations could have on the various stages of antigen processing. Correlations between positively selected residues and mean CD4 counts also allowed study of the effect of mutation on HIV disease progression. A number of mutations that could create or destroy proteasomal cleavage sites or reduce binding affinity of the transport antigen processing protein, effectively hindering epitope presentation, were identified. Many mutations correlated with the presence of specific HLA alleles and with lower or higher CD4 counts. For instance, the mutation V190I in subtype A1-infected individuals is associated with HLA-B*5802 (<jats:italic>P<\/jats:italic>= 4.73 \u00d7 10<jats:sup>\u22124<\/jats:sup>), a rapid-progression allele according to other studies, and also to a decreased mean CD4 count (<jats:italic>P<\/jats:italic>= 0.019). Thus, V190I is a possible HLA escape mutant. This method classifies many positively selected mutations across the entire<jats:italic>gag<\/jats:italic>region according to their potential for immune escape and their effect on disease progression.<\/jats:p>","DOI":"10.1128\/jvi.02742-06","type":"journal-article","created":{"date-parts":[[2007,12,6]],"date-time":"2007-12-06T02:00:33Z","timestamp":1196906433000},"page":"1980-1992","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":25,"title":["An Integrative Bioinformatic Approach for Studying Escape Mutations in Human Immunodeficiency Virus Type 1<i>gag<\/i>in the Pumwani Sex Worker Cohort"],"prefix":"10.1128","volume":"82","author":[{"given":"Harold O.","family":"Peters","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, University of Manitoba, 730 William Avenue, Winnipeg, Manitoba, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark G.","family":"Mendoza","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, University of Manitoba, 730 William Avenue, Winnipeg, Manitoba, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rupert E.","family":"Capina","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, University of Manitoba, 730 William Avenue, Winnipeg, Manitoba, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, University of Manitoba, 730 William Avenue, Winnipeg, Manitoba, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojuan","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, University of Manitoba, 730 William Avenue, Winnipeg, Manitoba, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Gubbins","sequence":"additional","affiliation":[{"name":"Public Health Agency of Canada, Winnipeg, Manitoba, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nico J. 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