title: Comprehensive analysis of HIV Gag-specific IFN-gamma response in HIV-1- and HIV-2-infected asymptomatic patients from a clinical cohort in The Gambia.
abstract: Majority of HIV-2-infected individuals meet the criteria of long-term non-progressors. This has been linked to superior qualitative HIV-2-specific cellular immune responses that correlate with viral control. However, it is unknown whether this is due to frequent targeting of immunodominant Gag epitopes in HIV-2 than HIV-1 infection. We describe a comprehensive comparison of the magnitude, breadth and frequency of Gag responses and the degree of cross-recognition of frequently targeted, immunodominant Gag peptides in a cross-sectional study of asymptomatic HIV-1- and HIV-2-infected individuals. Fresh PBMC from 20 HIV-1- and 20 HIV-2-infected patients with similar CD4(+) T-cell counts (p=0.36) were stimulated with pools of HIV-1 and/or HIV-2 Gag peptides in an IFN-gamma ELISPOT assay. We found no difference in the cumulative magnitude of IFN-gamma responses (p=0.75) despite significantly lower plasma viral loads in HIV-2-infected people (p<0.0001). However, Gag211-290 was targeted with significantly higher magnitude in HIV-2-infected subjects (p=0.03) although this did not correlate with viral control. There was no difference in frequently targeted Gag peptides, the breadth, immunodominance or cross-recognition of Gag peptide pools between the two infections. This suggests that other factors may control viral replication in HIV-2 infection.
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK. Beatrice.Ondondo@bristol.ac.uk
authors.forename: Beatrice O
authors.initials: BO
authors.lastname: Ondondo
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Rowland-Jones
authors.forename: Lucy
authors.initials: L
authors.lastname: Dorrell
authors.forename: Kevin
authors.initials: K
authors.lastname: Peterson
authors.forename: Matthew
authors.initials: M
authors.lastname: Cotten
authors.forename: Hilton
authors.initials: H
authors.lastname: Whittle
authors.forename: Assan
authors.initials: A
authors.lastname: Jaye
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D002478:Cells, Cultured; D015331:Cohort Studies; D003429:Cross Reactions / Q000276:immunology; D005260:Female; D005714:Gambia / Q000453:epidemiology; D015683:Gene Products, gag / Q000737:chemistry / Q000276:immunology*; D015658:HIV Infections / Q000453:epidemiology* / Q000276:immunology*; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology*; D015498:HIV-2 / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology
chemical_list: D015683:Gene Products, gag; D010455:Peptides; D007371:Interferon-gamma