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Journal of Virology, August 2008, p. 7773-7789, Vol. 82, No. 16
0022-538X/08/$08.00+0     doi:10.1128/JVI.00695-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Virological Consequences of Early Events following Cell-Cell Contact between Human Immunodeficiency Virus Type 1-Infected and Uninfected CD4+ Cells{triangledown}

Eliana Ruggiero, Roberta Bona, Claudia Muratori, and Maurizio Federico*

Division of Pathogenesis of Retroviruses, National AIDS Center, Istituto Superiore di Sanità, Rome, Italy

Received 28 March 2008/ Accepted 19 May 2008

Human immunodeficiency virus type 1 (HIV-1)-infected cells transmit viral products to uninfected CD4+ cells very rapidly. However, the natures of the transmitted viral products and the mechanism of transmission, as well as the relative virological consequences, have not yet been fully clarified. We studied the virological events occurring a few hours after contact between HIV-1-infected and uninfected CD4+ cells using a coculture cell system in which the virus expression in target cells could be monitored through the induction of a green fluorescent protein reporter gene driven by HIV-1 long terminal repeats. Within 16 h of coculture, we observed two phenomena not related to the cell-free virus infection, i.e., the formation of donor-target cell fusions and a fusion-independent internalization of viral particles likely occurring at least in part through intercellular connections. Both events depended on the expression of Env and CD4 in donor and target cells, respectively, whereas the HIV-1 internalization required clathrin activity in target cells. Importantly, both phenomena were also observed in cocultures of primary CD4+ lymphocytes, while primary macrophages supported only HIV-1 endocytosis. By investigating the virological consequences of these events, we noticed that while fused cells released infectious HIV-1 particles, albeit with reduced efficiency compared with donor cells, no virus expression was detectable upon HIV-1 endocytosis in target cells. In sum, the HIV-1 transmission following contact between an HIV-1-infected and an uninfected CD4+ cell can occur through different mechanisms, leading to distinguishable virological outcomes.

* Corresponding author. Mailing address: National AIDS Center, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. Phone: 39-06-49903248. Fax: 39-06-49903002. E-mail: maurizio.federico{at}iss.it

{triangledown} Published ahead of print on 28 May 2008.

Journal of Virology, August 2008, p. 7773-7789, Vol. 82, No. 16
0022-538X/08/$08.00+0     doi:10.1128/JVI.00695-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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