title: Inhibition of HIV-1 replication in alveolar macrophages by adenovirus gene transfer vectors.
abstract: To assess the hypothesis that infection of alveolar macrophages (AM) with adenovirus (Ad) gene transfer vectors might prevent subsequent human immunodeficiency virus (HIV)-1 replication in AM, AM isolated from normal volunteers were infected with increasing doses of first generation (E1(-)) Ad vectors, followed 72 h later by infection with HIV-1(JRFL), an R5/M-tropic strain that preferentially uses the CCR5 coreceptor. As a measure of HIV-1 replication, p24 Ag was quantified by enzyme-linked imunosorbent assay in supernatants on Days 4 to 14 after HIV-1infection. Pretreatment of the AM with an Ad vector resulted in a dose- and time-dependent suppression of subsequent HIV-1 replication. The Ad vector inhibition of HIV-1 replication was independent of the transgene in the Ad vector expression cassette and E4 genes in the Ad backbone. Moreover, it did not appear to be secondary to a soluble factor released by the AM, nor was it overridden by the concomitant transfer of the CCR5 or CXCR4 receptors to the AM before HIV-1 infection. These observations have implications regarding pulmonary host responses associated with HIV-1 infection, as well as possibly uncovering new therapeutic strategies against HIV-1 infection.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Microbiology and Immunology, and Institute of Genetic Medicine, Weill Medical College of Cornell University, New York 10021, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Rice
authors.forename: Ruth
authors.initials: R
authors.lastname: Connor
authors.forename: Stefan
authors.initials: S
authors.lastname: Worgall
authors.forename: John P
authors.initials: JP
authors.lastname: Moore
authors.forename: Philip L
authors.initials: PL
authors.lastname: Leopold
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kaner
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000821:virology*; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D019076:Transgenes; D014779:Virus Replication
chemical_list: D019713:Receptors, CCR5; D019718:Receptors, CXCR4