Inhibition of HIV-1 replication in alveolar macrophages by adenovirus gene transfer vectors.
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.
Rice
Joshua
J
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.
Connor
Ruth
R
Worgall
Stefan
S
Moore
John P
JP
Leopold
Philip L
PL
Kaner
Robert J
RJ
Crystal
Ronald G
RG
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
D019713:Receptors, CCR5; D019718:Receptors, CXCR4