Inhibition of HIV-1 replication in alveolar macrophages by adenovirus gene transfer vectors.
| Publication Type | Academic Article |
| Authors | Rice J, Connor R, Worgall S, Moore J, Leopold P, Kaner R, Crystal R |
| Journal | Am J Respir Cell Mol Biol |
| Volume | 27 |
| Issue | 2 |
| Pagination | 214-9 |
| Date Published | 08/01/2002 |
| ISSN | 1044-1549 |
| Keywords | Adenoviridae, Genetic Vectors, HIV-1, Macrophages, Alveolar, Virus Replication |
| 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. |
| DOI | 10.1165/ajrcmb.27.2.4696 |
| PubMed ID | 12151313 |