Monocyte-derived macrophages (M/M) are considered the second cellular target of HIV-1 and a crucial virus reservoir. M/M are widely distributed in all tissues and organs, including the CNS, where they represent the most common HIV-infected cells. Differently from activated CD4+ T lymphocytes, M/M are resistant to the cytopathic effect of HIV and survive HIV infection for a long lime. Moreover, HIV-1 replication in M/M is a key pathogenetic event during the course of HIV-1 infection. Overall findings strongly support the clinical relevance of anti-HIV drugs in M/M. Nucleoside RT inhibitors (NRTIs) are more active against HIV in M/M than in CD4+ T lymphocytes. Their activity is further boosted by the presence of an additional monophosphate group (i.e., a phosphonate group, as in the case of Tenofovir), thus overcoming the bottleneck of the low phosphorylation ability of M/M. In contrast, the antiviral activity of non-NRTIs (not affecting the DNA chain elongation) in M/M is similar to that in CD4+ T lymphocytes. Protease inhibitors are the only clinically approved drugs acting at a late stage of the HIV lifecycle. They are able to interfere with HIV replication in HIV-1 chronically infected M/M, even if at concentrations greater than those observed in HIV-1 chronically infected CD4+ T lymphocytes. Finally, several new drugs have been shown to interfere efficiently with HIV replication in M/M, including entry inhibitors. A better understanding of the activity of the anti-HIV drugs in M/M may represent a key element for the design of effective anti-HIV chemotherapy. Â© Society for Leukocyte Biology.
Aquaro, S., Svicher, V., Schols, D., Pollicita, M., Antinori, A., Balzarini, J., et al. (2006). Mechanisms underlying activity of antiretroviral drugs in HIV-1-infected macrophages: New therapeutic strategies. JOURNAL OF LEUKOCYTE BIOLOGY, 80(5), 1103-1110 [10.1189/jlb.0606376].
|Tipologia:||Articolo su rivista|
|Citazione:||Aquaro, S., Svicher, V., Schols, D., Pollicita, M., Antinori, A., Balzarini, J., et al. (2006). Mechanisms underlying activity of antiretroviral drugs in HIV-1-infected macrophages: New therapeutic strategies. JOURNAL OF LEUKOCYTE BIOLOGY, 80(5), 1103-1110 [10.1189/jlb.0606376].|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore MED/07 - Microbiologia e Microbiologia Clinica|
|Revisione (peer review):||Sì, ma tipo non specificato|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1189/jlb.0606376|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2006|
|Titolo:||Mechanisms underlying activity of antiretroviral drugs in HIV-1-infected macrophages: New therapeutic strategies|
|Autori:||Aquaro, S; Svicher, V; Schols, D; Pollicita, M; Antinori, A; Balzarini, J; Perno, CF|
|Appare nelle tipologie:||01 - Articolo su rivista|