title: High frequency of transmitted HIV-1 Gag HLA class I-driven immune escape variants but minimal immune selection over the first year of clade C infection.
abstract: In chronic HIV infection, CD8+ T cell responses to Gag are associated with lower viral loads, but longitudinal studies of HLA-restricted CD8+ T cell-driven selection pressure in Gag from the time of acute infection are limited. In this study we examined Gag sequence evolution over the first year of infection in 22 patients identified prior to seroconversion. A total of 310 and 337 full-length Gag sequences from the earliest available samples (median = 14 days after infection [Fiebig stage I/II]) and at one-year post infection respectively were generated. Six of 22 (27%) individuals were infected with multiple variants. There was a trend towards early intra-patient viral sequence diversity correlating with viral load set point (p = 0.07, r = 0.39). At 14 days post infection, 59.7% of Gag CTL epitopes contained non-consensus polymorphisms and over half of these (35.3%) comprised of previously described CTL escape variants. Consensus and variant CTL epitope proportions were equally distributed irrespective of the selecting host HLA allele and most epitopes remained unchanged over 12 months post infection. These data suggest that intrapatient diversity during acute infection is an indicator of disease outcome. In this setting, there is a high rate of transmitted CTL escape variants and limited immune selection in Gag during the first year of infection. These data have relevance for vaccine strategies designed to elicit effective CD8+ T cell immune responses.
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Durban, South Africa; KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Durban, South Africa.
authors.forename: Kamini
authors.initials: K
authors.lastname: Gounder
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Durban, South Africa; KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Durban, South Africa.
authors.forename: Nagavelli
authors.initials: N
authors.lastname: Padayachi
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Durban, South Africa; KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Durban, South Africa.
authors.forename: Jaclyn K
authors.initials: JK
authors.lastname: Mann
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Durban, South Africa; KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Durban, South Africa.
authors.forename: Mopo
authors.initials: M
authors.lastname: Radebe
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Durban, South Africa; KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Durban, South Africa.
authors.forename: Mammekwa
authors.initials: M
authors.lastname: Mokgoro
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Durban, South Africa; KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Durban, South Africa.
authors.forename: Mary
authors.initials: M
authors.lastname: van der Stok
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Durban, South Africa; KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Durban, South Africa.
authors.forename: Lungile
authors.initials: L
authors.lastname: Mkhize
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Durban, South Africa; KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Durban, South Africa.
authors.forename: Zenele
authors.initials: Z
authors.lastname: Mncube
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Durban, South Africa; KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Durban, South Africa.
authors.forename: Manjeetha
authors.initials: M
authors.lastname: Jaggernath
authors.affiliation: Biostatistics Unit, Medical Research Council, 491 Peter Mokaba Road, Overport, Durban, South Africa.
authors.forename: Tarylee
authors.initials: T
authors.lastname: Reddy
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Durban, South Africa; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, Boston, Massachusetts, United States of America; Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD, United States of America.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Durban, South Africa; KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Durban, South Africa; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, Boston, Massachusetts, United States of America; Max Planck Institute for Infection Biology, Charitestraße 1, Berlin, Germany.
authors.forename: Thumbi
authors.initials: T
authors.lastname: Ndung'u
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D005260:Female; D005787:Gene Frequency; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D012641:Selection, Genetic; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology
chemical_list: D006680:HLA Antigens; D054301:gag Gene Products, Human Immunodeficiency Virus