title: Cytoskeletal proteins bound to heat-shock protein 70 may elicit resistance to simian immunodeficiency virus infection of CD4(+) T cells.
abstract: This study is based on the evidence that immunization of macaques with human CD4(+) T cells elicits prevention of simian immunodeficiency virus (SIV) infection. We hypothesized that heat-shock protein 70 (HSP70) isolated from CD4(+) T cells may act as a chaperone and carry the protective host proteins. Two moieties of HSP70 were affinity-purified from human CD4(+) T cells; an ADP preparation with HSP70-bound proteins (ADP-HSP) and an ATP control preparation. Immunization of rhesus macaques with these preparations showed significant inhibition of SIVmac251 infectivity ex vivo in CD4(+) T cells only with the ADP-HSP (P = 0.01). Proteomic analysis identified three cytoskeletal elements, cofilin, profilin and gamma-actin, exclusively in the ADP-HSP preparation. Investigation of the mechanism of prevention of SIV replication suggests that antibodies to the cytoskeletal proteins may inhibit actin depolymerization and facilitate viral degradation by the innate antiviral APOBEC3G. As cytoskeletal proteins are critical in the formation of virological and immunological synapses, finding specific antibodies and anti-SIV/human immunodeficiency virus (HIV) factors suggests a novel insight into HIV-1 immunopathogenesis.
authors.affiliation: Mucosal Immunology Unit, Kings College London, Guy's Hospital, London, UK.
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Bergmeier
authors.forename: Kaboutar
authors.initials: K
authors.lastname: Babaahmady
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Pido-Lopez
authors.forename: Kate J
authors.initials: KJ
authors.lastname: Heesom
authors.forename: Charles G
authors.initials: CG
authors.lastname: Kelly
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehner
mesh_terms: D000071480:APOBEC-3G Deaminase; D051339:Actin Depolymerizing Factors / Q000737:chemistry / Q000378:metabolism*; D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D003564:Cytidine Deaminase / Q000276:immunology; D015180:Electrophoresis, Gel, Two-Dimensional; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D008251:Macaca; D013058:Mass Spectrometry; D009500:Neutralization Tests; D051304:Profilins / Q000737:chemistry / Q000378:metabolism*; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000302:isolation & purification; D014779:Virus Replication / Q000276:immunology
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D018840:HSP70 Heat-Shock Proteins; D051304:Profilins; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase