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Journal of Virology, September 2007, p. 9078-9087, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00675-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Macrophages Transmit Human Immunodeficiency Virus Type 1 Products to CD4-Negative Cells: Involvement of Matrix Metalloproteinase 9{triangledown}

Claudia Muratori,1 Antonella Sistigu,1 Eliana Ruggiero,1 Mario Falchi,1 Ilaria Bacigalupo,2 Clelia Palladino,2 Elena Toschi,2 and Maurizio Federico1*

Division of Pathogenesis of Retroviruses,1 Virus-Host Interaction and Core-Laboratory of Immunology, National AIDS Center, Istituto Superiore di Sanità, Rome, Italy2

Received 29 March 2007/ Accepted 11 June 2007

It was previously reported that human immunodeficiency virus type 1 (HIV-1) spreads in CD4 lymphocytes through cell-to-cell transmission. Here we report that HIV-1-infected macrophages, but not lymphocytes, transmit HIV-1 products to CD4-negative cells of either epithelial, neuronal, or endothelial origin in the absence of overt HIV-1 infection. This phenomenon was detectable as early as 1 h after the start of cocultivation and depended on cell-to-cell contact but not on the release of viral particles from donor cells. Transfer of HIV-1 products occurred upon their polarization and colocalization within zones of cell-to-cell contact similar to virological synapses. Neither HIV-1 Env nor Nef expression was required but, interestingly, we found that an HIV-1-dependent increase in matrix metalloproteinase 9 production from donor cells significantly contributed to the cell-to-cell transmission of the viral products. The macrophage-driven transfer of HIV-1 products to diverse CD4-negative cell types may have a significant role in AIDS pathogenesis.

* 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 20 June 2007.

Journal of Virology, September 2007, p. 9078-9087, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00675-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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