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Adenovirus Vectors Block HIV-1 Replication in Human Alveolar Macrophages by Inhibition of the LTR
American Journal of Respiratory Cell and Molecular Biology, 10/07/09
Kaner RJ et al. – The data indicate that Ad vectors are inhibitory to HIV–1 replication in human AM based in part, on their ability to inhibit LTR–driven transcription.
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Robert J. Kaner, 10/09/09
Robert J. Kaner, 10/09/09
| Heterologous viruses may be stimulatory or inhibitory to viral replication. Evaluation of adenoviral vector (Ad) based HIV-1 vaccines as part of clinical strategies to reduce the burden of HIV-1 disease raises the issue of potential effects of Ad itself on HIV-1 replication in immune system cells. Since macrophages are a known reservoir of HIV-1, we studied the effects of Ad vectors on HIV-1 replication in human alveolar macrophages in vitro. We observed that Ad is inhibitory to HIV-1 replication in AM. In systematically analyzing the steps in the HIV-1 lifecycle, we determined that HIV-1 replication is being blocked at the level of HIV-1 long terminal repeat (LTR) transcription. Since this effect is not mediated by soluble factors and Ad DNA is absolutely required, we evaluated interferon-related intracellular signal transduction pathways. STAT-1 phosphorylation and IRF-8 protein levels were upregulated indicating the inhibitory effect of Ad on HIV-1 replication in AM is likely mediated via intracellular interferon pathway signaling. |
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