Dynamics and timing of in vivo mutations at Gag residue 242 during primary HIV-1 subtype C infection.
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Publication Details
Author list: Novitsky V, Wang R, Margolin L, Baca J, Moyo S, Musonda R, Essex M
Publisher: Elsevier
Publication year: 2010
Journal: Virology (0042-6822)
Journal acronym: Virology
Volume number: 403
Issue number: 1
Start page: 37
End page: 46
Number of pages: 10
ISSN: 0042-6822
Languages: English-Great Britain (EN-GB)
Abstract
Viral mutations at Gag residue 242 and relevant viral polymorphisms were analyzed in a cohort of 42 individuals with primary HIV-1 subtype C infection using single-genome amplification/sequencing. In HLA-B*57/5801-negative subjects infected with 242N escape variant, reversion to Asn appeared at median (IQR) 103 days (97-213 days) post-seroconversion (p/s) and became dominant at 193 days (170-215 days) p/s. In subjects expressing HLA-B*57/5801 and infected with the wild-type virus, the T242N escape appeared at 203 days (196-231) p/s, reached dominance at 277 days (265-315 days) p/s, and became complete at 323 days (289-373 days) p/s. HLA-B*57/5801-negative subjects infected with 242N escape variant did not show reduced viral load or increased CD4 count. The study highlights the differential selection of T242N escape by HLA-B*57 and B*5801 and suggests that the presence of HLA-B*57/5801-mediated immune pressure is able to control replication of the wild-type virus encoding Thr at Gag residue 242 but fails to suppress the T242N escape variant.
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