title: The heat-shock protein receptor CD91 is up-regulated in monocytes of HIV-1-infected "true" long-term nonprogressors.
abstract: A small proportion of patients with human immunodeficiency virus type 1 (HIV-1) remains asymptomatic for a long period after infection. It is thought that a vigorous immune response may contribute to long-term nonprogression, though studies are confounded by heterogeneity among patients. We studied the levels of HIV-1 receptors, costimulatory T-cell molecules, and dendritic cell (DC) numbers in 18 patients with long-term infection, CD4 counts greater than 400 cells/mm(3), and HIV-1 viral loads lower than 50 copies/mL. These patients were further differentiated through the presence or absence of 2-LTR DNA circles, a possible marker for residual ongoing HIV-1 replication. A statistically significant increase in levels of CD91, the heat-shock protein (HSP) receptor, was observed in therapy-naive patients who had no evidence of ongoing viral replication (P =.01). This difference was most notable on their monocytes. High levels of CD91 may be a host factor that contributes to the maintenance of long-term nonprogression. The ability of CD91 to internalize alpha-defensins and to cross-present exogenous antigen to cytotoxic T lymphocytes through major histocompatibility complex (MHC) class 1 may maintain CD8(+) responses in these patients.
authors.affiliation: Department of Immunology, Division of Investigative Science, Faculty of Medicine, Imperial College of Science, Technology and Medicine, The Chelsea and Westminster Hospital, London, United Kingdom. j.stebbing@ic.ac.uk
authors.forename: Justin
authors.initials: J
authors.lastname: Stebbing
authors.forename: Brian
authors.initials: B
authors.lastname: Gazzard
authors.forename: Louise
authors.initials: L
authors.lastname: Kim
authors.forename: Simon
authors.initials: S
authors.lastname: Portsmouth
authors.forename: Adrian
authors.initials: A
authors.lastname: Wildfire
authors.forename: Ian
authors.initials: I
authors.lastname: Teo
authors.forename: Mark
authors.initials: M
authors.lastname: Nelson
authors.forename: Mark
authors.initials: M
authors.lastname: Bower
authors.forename: Frances
authors.initials: F
authors.lastname: Gotch
authors.forename: Sunil
authors.initials: S
authors.lastname: Shaunak
authors.forename: Pramod
authors.initials: P
authors.lastname: Srivastava
authors.forename: Steve
authors.initials: S
authors.lastname: Patterson
mesh_terms: D015703:Antigens, CD / Q000235:genetics*; D001483:Base Sequence; D018791:CD4 Lymphocyte Count; D017931:DNA Primers; D003713:Dendritic Cells / Q000276:immunology*; D018450:Disease Progression; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008297:Male; D009000:Monocytes / Q000276:immunology*; D012367:RNA, Viral / Q000097:blood; D017741:Survivors; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D019562:Viral Load
chemical_list: D015703:Antigens, CD; D017931:DNA Primers; C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D012367:RNA, Viral