title: Alcohol enhances HIV type 1 infection in normal human oral keratinocytes by up-regulating cell-surface CXCR4 coreceptor.
abstract: Recent studies suggest that normal human oral keratinocytes (NHOKs) can be infected by HIV-1, and alcohol can enhance HIV infection and replication in lymphocytes. In this study, we examined the possibility that alcohol might facilitate HIV-1 infection of NHOKs by up-regulating cell surface expression of the coreceptor, CXCR4. Alcohol enhanced in vitro infection of NHOKs by CXCR4-tropic strains of HIV-1 as indicated by synthesis of viral reverse transcripts and production of p24gag protein. Alcohol had no effect on CXCR4 gene expression or on total cellular complements of CXCR4 protein. However, alcohol did enhance the fraction of total CXCR4 expressed on the cell surface relative to intracellular stores. Alcohol-induced up-regulation of cell surface CXCR4 expression and HIV-1 infectivity could be blocked by SDF-1alpha-mediated internalization. These data suggest that alcohol may influence oral HIV transmission by altering the cellular compartmentalization of CXCR4 in cells of the oral cavity.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Charles R. Drew University of Medicine and Science, Los Angeles, California 90059, USA.
authors.forename: Hongying
authors.initials: H
authors.lastname: Chen
authors.forename: Junli
authors.initials: J
authors.lastname: Zha
authors.forename: Reginald E
authors.initials: RE
authors.lastname: Gowans
authors.forename: Paulo
authors.initials: P
authors.lastname: Camargo
authors.forename: Junko
authors.initials: J
authors.lastname: Nishitani
authors.forename: Joseph L
authors.initials: JL
authors.lastname: McQuirter
authors.forename: Steve W
authors.initials: SW
authors.lastname: Cole
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Zack
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D004279:DNA, Viral / Q000235:genetics; D000431:Ethanol / Q000494:pharmacology*; D005434:Flow Cytometry; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D009055:Mouth / Q000166:cytology* / Q000378:metabolism / Q000821:virology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D019718:Receptors, CXCR4 / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D017931:DNA Primers; D004279:DNA, Viral; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D000431:Ethanol