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• W2091575797 abstract "E1 adenovirus (Ad) vector infection of human alveolar macrophages (AM) inhibits HIV-1 replication independently of any transgene (Rice et al, Am J Respir Cell Mol Biol 2002; 27: 214-219) when the AM are infected with HIV-1 in vitro. We have previously shown that deletions of E4, Ad DNA polymerase or preterminal protein had no effect on the ability of Ad to block HIV-1 replication, empty Ad capsids do not block HIV-1 replication, and Ad acts, in part, by suppressing transcription from the HIV-1 long terminal repeats (LTR). The inhibition of HIV-1 replication by Ad is dose-dependent. We hypothesized that Ad would cause a similar dose-dependent inhibition of endogenous HIV-1 replication in AM obtained from HIV-1+ individuals. To address this question, we examined the shape of the dose-response curve for submaximal Ad inhibition of HIV-1 replication in AM. AM (6|[times]|105 cells/well) from a normal individual were infected with AdNull (0 to 2.5 |[times]| 104 pu/cell) or treated with azidothymidine (AZT, 10 |[mu]|g/ml), prior to infection with HIV-1 (103 TCID50/well). Conditioned media was collected twice weekly, and HIV-1 replication was quantified by measuring p24 in the conditioned media by ELISA. On day 16 post-infection, at a time of linear increases in p24, indicating active HIV-1 replication, p24 levels were (ng/ml) No Ad: 19.4; Ad doses in pu/cell: 102: 17.2 ; 5|[times]|102: 12.5; 103: 5.2; 5|[times]|103: 0.72; 104 0.11; 2.5|[times]|104: 0.04; AZT: 0.04. We compared these results with Ad effects on HIV-1 spontaneously elaborated from AM recovered from an HIV-1 positive individual. AM (8 |[times]| 105 cells/well) were infected with AdNull (0 to 2.5 |[times]| 104 pu/cell) or treated with AZT. p24 levels in the culture increased linearly over 4 days. On day 4 post-infection with Ad, p24 levels were No Ad: 44.2; 102: 32.4 ; 5|[times]|102: 24.7; 103: 10.7; 5|[times]|103: 1.70; 104: 0.27; 2.5|[times]|104: 0.08; AZT: 0.08. The dose-response for inhibitory effects of Ad on HIV-1 replication was similar under both conditions over several logs of Ad doses. In a separate experiment, Ad inhibition of HIV-1 replication in AM obtained from another HIV+ individual was evaluated as a function of Ad dose in half-log increments spanning the range from 102 |[minus]|3|[times]|104 pu/cell and yielding a range of p24 levels on day 4 ranging from 1.1-26.2. When the percent inhibition of HIV-1 replication was plotted as a function of log [Ad dose], the relationship was nearly linear, R2=0.96 over a 2 log range of doses. These data indicate that Ad inhibits endogenous HIV-1 replication in AM with a dose-response relationship similar to that observed when normal AM are infected with HIV-1 in vitro." @default.
• W2091575797 created "2016-06-24" @default.
• W2091575797 date "2005-05-01" @default.
• W2091575797 modified "2023-09-26" @default.
• W2091575797 title "994. E1 Adenovirus Gene Transfer Vectors Inhibit HIV-1 Replication in Human Alveolar Macrophages" @default.
• W2091575797 doi "https://doi.org/10.1016/j.ymthe.2005.07.541" @default.
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