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Journal of Virology, January 2007, p. 708-717, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.01367-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Viral Interactions in Human Lymphoid Tissue: Human Herpesvirus 7 Suppresses the Replication of CCR5-Tropic Human Immunodeficiency Virus Type 1 via CD4 Modulation{triangledown}

Andrea Lisco,1 Jean-Charles Grivel,1 Angélique Biancotto,1 Christophe Vanpouille,1 Francesco Origgi,2 Mauro S. Malnati,2 Dominique Schols,4 Paolo Lusso,2,3* and Leonid B. Margolis1*

Laboratory of Molecular and Cellular Biophysics, National Institute of Child Health and Human Development, Bethesda, Maryland 20892,1 Unit of Human Virology, DIBIT San Raffaele Scientific Institute, Milano, Italy,2 Department of Medical Sciences, University of Cagliari Medical School, Cagliari, Italy,3 Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium4

Received 28 June 2006/ Accepted 16 October 2006

Human immunodeficiency virus (HIV) infection is often accompanied by infection with other pathogens that affect the clinical course of HIV disease. Here, we identified another virus, human herpesvirus 7 (HHV-7) that interferes with HIV type 1 (HIV-1) replication in human lymphoid tissue, where critical events of HIV disease occur. Like the closely related HHV-6, HHV-7 suppresses the replication of CCR5-tropic (R5) HIV-1 in coinfected blocks of human lymphoid tissue. Unlike HHV-6, which affects HIV-1 by upregulating RANTES, HHV-7 did not upregulate any CCR5-binding chemokine. Rather, the inhibition of R5 HIV-1 by HHV-7 was associated with a marked downregulation of CD4, the cellular receptor shared by HHV-7 and HIV-1. HHV-7-induced CD4 downregulation was sufficient for HIV-1 inhibition, since comparable downregulation of CD4 with cyclotriazadisulfonamide, a synthetic macrocycle that specifically modulates expression of CD4, resulted in the suppression of HIV infection similar to that seen in HHV-7-infected tissues. In contrast to R5 HIV-1, CXCR4-tropic (X4) HIV-1 was only minimally suppressed by HHV-7 coinfection. This selectivity in suppression of R5 and X4 HIV-1 is explained by a suppression of HHV-7 replication in X4- but not in R5-coinfected tissues. These results suggest that HIV-1 and HHV-7 may interfere in lymphoid tissue in vivo, thus potentially affecting the progression of HIV-1 disease. Knowledge of the mechanisms of interaction of HIV-1 with HHV-7, as well as with other pathogens that modulate HIV-1 replication, may provide new insights into HIV pathogenesis and lead to the development of new anti-HIV therapeutic strategies.

* Corresponding author. Mailing address for L. Margolis: Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, NIH, Bldg. 10, Rm. 9D58, 9000 Rockville Pike, Bethesda, MD 20892. Phone: (301) 594-2476. Fax: (301) 480-0857. E-mail: margolis{at}helix.nih.gov. Mailing address for P. Lusso: DIBIT- San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, Italy. Phone: 39-02-2643282. Fax: 39-02-26434905. E-mail: paolo.lusso{at}hsr.it.

{triangledown} Published ahead of print on 25 October 2006.

Journal of Virology, January 2007, p. 708-717, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.01367-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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