title: Adaptive changes in HIV-1 subtype C proteins during early infection are driven by changes in HLA-associated immune pressure.
abstract: It is unresolved whether recently transmitted human immunodeficiency viruses (HIV) have genetic features that specifically favour their transmissibility. To identify potential "transmission signatures", we compared 20 full-length HIV-1 subtype C genomes from primary infections, with 66 sampled from ethnically and geographically matched individuals with chronic infections. Controlling for recombination and phylogenetic relatedness, we identified 39 sites at which amino acid frequency spectra differed significantly between groups. These sites were predominantly located within Env, Pol and Gag (14/39, 9/39 and 6/39 respectively) and were significantly clustered (33/39) within known immunoreactive peptides. Within 6 months of infection, we detected reversion-to-consensus mutations at 14 sites and potential CTL escape mutations at seven. Here we provide evidence that frequent reversion mutations probably allows the virus to recover replicative fitness which, together with immune escape driven by the HLA alleles of the new hosts, differentiate sequences from chronic infections from those sampled shortly after transmission.
authors.affiliation: Institute of Infectious Diseases and Molecular Medicine (IIDMM), Division of Medical Virology, University of Cape Town, South Africa.
authors.forename: F K
authors.initials: FK
authors.lastname: Treurnicht
authors.forename: C
authors.initials: C
authors.lastname: Seoighe
authors.forename: D P
authors.initials: DP
authors.lastname: Martin
authors.forename: N
authors.initials: N
authors.lastname: Wood
authors.forename: M-R
authors.initials: MR
authors.lastname: Abrahams
authors.forename: D de Assis
authors.initials: Dde A
authors.lastname: Rosa
authors.forename: H
authors.initials: H
authors.lastname: Bredell
authors.forename: Z
authors.initials: Z
authors.lastname: Woodman
authors.forename: W
authors.initials: W
authors.lastname: Hide
authors.forename: K
authors.initials: K
authors.lastname: Mlisana
authors.forename: S Abdool
authors.initials: SA
authors.lastname: Karim
authors.forename: C M
authors.initials: CM
authors.lastname: Gray
authors.forename: C
authors.initials: C
authors.lastname: Williamson
mesh_terms: D019943:Amino Acid Substitution; D018450:Disease Progression; D005260:Female; D016679:Genome, Viral / Q000235:genetics; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D006680:HLA Antigens; D014759:Viral Envelope Proteins