Abstract |
Sexual transmission is now the most frequent means of diffusion of human immunodeficiency virus type 1 (HIV-1). Even if the underlying mechanism is still largely unknown, there is a consensus regarding the key role played by mucosal dendritic cells (DCs) in capturing HIV through contact with infected subepithelial lymphocytes, and their capacity to spread HIV by trans- infection. We found that HIV protease inhibitors (PIs) reduced virion endocytosis strongly in monocyte-derived immature (i) DCs contacting HIV-1-infected cells, and that this phenomenon led to dramatically impaired trans- infection activity. This inhibitory effect was not mediated by the block of viral protease activity, as it was also operative when donor cells were infected with a PI-resistant HIV-1 strain. The block of virus maturation imposed by PIs did not correlate with significant variations in the levels of virus expression in donor cells or of Gag/Env virion incorporation. Also, PIs did not affect the endocytosis activity of DCs. In contrast, we noticed that PI treatment inhibited the formation of cell-cell conjugates whilst reducing the expression of ICAM-1 in target iDCs. Our results contribute to a better delineation of the mechanisms underlying HIV-1 trans- infection activity in DCs, whilst having implications for the development of new anti-HIV microbicide strategies.
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Authors | Claudia Muratori, Eliana Ruggiero, Antonella Sistigu, Roberta Bona, Maurizio Federico |
Journal | The Journal of general virology
(J Gen Virol)
Vol. 90
Issue Pt 11
Pg. 2777-2787
(Nov 2009)
ISSN: 1465-2099 [Electronic] England |
PMID | 19625465
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- HIV Protease Inhibitors
- Intercellular Adhesion Molecule-1
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Topics |
- Animals
- Cell Adhesion
(drug effects)
- Cell Line
- Cells, Cultured
- Coculture Techniques
- Dendritic Cells
(physiology, virology)
- Endocytosis
- HIV Protease Inhibitors
(pharmacology)
- HIV-1
(drug effects)
- Humans
- Intercellular Adhesion Molecule-1
(biosynthesis)
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