Dynamics and timing of in vivo mutations at Gag residue 242 during primary HIV-1 subtype C infection

Virology. 2010 Jul 20;403(1):37-46. doi: 10.1016/j.virol.2010.04.001. Epub 2010 May 4.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Animals
  • Female
  • HIV Infections / virology*
  • HIV-1 / genetics*
  • HIV-1 / immunology*
  • HIV-1 / isolation & purification
  • HLA-B Antigens / genetics
  • Humans
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Point Mutation
  • Polymorphism, Genetic*
  • Selection, Genetic
  • Suppression, Genetic
  • Time Factors
  • Young Adult
  • gag Gene Products, Human Immunodeficiency Virus / genetics*
  • gag Gene Products, Human Immunodeficiency Virus / immunology*

Substances

  • HLA-B Antigens
  • HLA-B*58:01 antigen
  • HLA-B57 antigen
  • gag Gene Products, Human Immunodeficiency Virus