title: Dynamics and timing of in vivo mutations at Gag residue 242 during primary HIV-1 subtype C infection.
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.
authors.affiliation: Harvard School of Public Health AIDS Initiative, Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Novitsky
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Lauren
authors.initials: L
authors.lastname: Margolin
authors.forename: Jeannie
authors.initials: J
authors.lastname: Baca
authors.forename: Sikhulile
authors.initials: S
authors.lastname: Moyo
authors.forename: Rosemary
authors.initials: R
authors.lastname: Musonda
authors.forename: M
authors.initials: M
authors.lastname: Essex
mesh_terms: D000328:Adult; D000818:Animals; D005260:Female; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification; D015235:HLA-B Antigens / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012641:Selection, Genetic; D013489:Suppression, Genetic; D013997:Time Factors; D055815:Young Adult; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology*
chemical_list: D015235:HLA-B Antigens; C500126:HLA-B*58:01 antigen; C103707:HLA-B57 antigen; D054301:gag Gene Products, Human Immunodeficiency Virus
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