title: Expression of the common heat-shock protein receptor CD91 is increased on monocytes of exposed yet HIV-1-seronegative subjects.
abstract: The significantly higher surface expression of the surface heat-shock protein receptor CD91 on monocytes of human immunodeficiency virus type-1 (HIV-1)-infected, long-term nonprogressors suggests that HIV-1 antigen uptake and cross-presentation mediated by CD91 may contribute to host anti-HIV-1 defenses and play a role in protection against HIV-1 infection. To investigate this further, we performed phenotypic analysis to compare CD91 surface expression on CD14(+) monocytes derived from a cohort of HIV-1-exposed seronegative (ESN) subjects, their seropositive (SP) partners, and healthy HIV-1-unexposed seronegative (USN) subjects. The median fluorescent intensity (MFI) of CD91 on CD14(+) monocytes was significantly higher in ESN compared with SP (P = 0.028) or USN (P = 0.007), as well as in SP compared with USN subjects (P = 0.018). CD91 MFI was not normalized in SP subjects on highly active antiretroviral therapy (HAART) despite sustainable, undetectable plasma viraemia. Data in three SP subjects experiencing viral rebounds following interruption of HAART showed low CD91 MFI comparable with levels in USN subjects. There was a significant positive correlation between CD91 MFI and CD8(+) T cell counts in HAART-naïve SP subjects (r = 0.7, P = 0.015). Increased surface expression of CD91 on CD14(+) monocytes is associated with the apparent HIV-1 resistance that is observed in ESN subjects.
authors.affiliation: Department of Immunology, Imperial College, Chelsea & Westminster Hospital, London, UK. a.kebba@ic.ac.uk
authors.forename: Anthony
authors.initials: A
authors.lastname: Kebba
authors.forename: Justin
authors.initials: J
authors.lastname: Stebbing
authors.forename: Samantha
authors.initials: S
authors.lastname: Rowland
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ingram
authors.forename: John
authors.initials: J
authors.lastname: Agaba
authors.forename: Steve
authors.initials: S
authors.lastname: Patterson
authors.forename: Pontiano
authors.initials: P
authors.lastname: Kaleebu
authors.forename: Nesrina
authors.initials: N
authors.lastname: Imami
authors.forename: Frances
authors.initials: F
authors.lastname: Gotch
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology*; D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D015488:HIV Antigens / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D018023:HIV Seronegativity / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D015488:HIV Antigens; C475476:LRP1 protein, human; D018950:Lipopolysaccharide Receptors; D026503:Low Density Lipoprotein Receptor-Related Protein-1