title: Pathogenic prion protein fragment (PrP106-126) promotes human immunodeficiency virus type-1 infection in peripheral blood monocyte-derived macrophages.
abstract: Transfusion of blood and blood products contaminated with the pathogenic form of prion protein Prp(sc), thought to be the causative agent of variant a Creutzfeldt-Jakob disease (vCJD), may result in serious consequences in recipients with a compromised immune system, for example, as seen in HIV-1 infection. In the present study, we demonstrate that treatment of peripheral blood monocyte-derived macrophages (MDM) with PrP106-126, a synthetic domain of PrP(sc) that has intrinsic functional activities related to the full-length protein, markedly increased their susceptibility to HIV-1 infection, induced cytokine secretion, and enhanced their migratory behavior in response to N-formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLP). Live-cell imaging of MDM cultured in the presence of PrP106-126 showed large cell clusters indicative of cellular activation. Tyrosine kinase inhibitor STI-571, protein kinase C inhibitor K252B, and cyclin-dependent kinase inhibitor olomoucine attenuated PrP106-126-induced altered MDM functions. These findings delineate a previously undefined functional role of PrP106-126-mediated host cell response in promoting HIV-1 pathogenesis.
authors.affiliation: Division of Monoclonal Antibodies, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA.
authors.forename: Silvia M
authors.initials: SM
authors.lastname: Bacot
authors.affiliation: Division of Monoclonal Antibodies, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA.
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Feldman
authors.affiliation: National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Yamada
authors.affiliation: Division of Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA. Electronic address: subhash.dhawan@fda.hhs.gov.
authors.forename: Subhash
authors.initials: S
authors.lastname: Dhawan
mesh_terms: D002478:Cells, Cultured; D015658:HIV Infections / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000821:virology*; D009000:Monocytes / Q000821:virology*; D018620:PrPSc Proteins / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D018620:PrPSc Proteins
keywords: Blood; HIV-1; Macrophages; Peripheral blood monocytes; Prion protein