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Journal of Virology, November 2005, p. 14318-14329, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.14318-14329.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Human ß-Defensins Suppress Human Immunodeficiency Virus Infection: Potential Role in Mucosal Protection{dagger}

Lingling Sun,1 Catherine M. Finnegan,2 Tina Kish-Catalone,1,§ Robert Blumenthal,2 Paolo Garzino-Demo,3 Gian M. La Terra Maggiore,3 Sid Berrone,3 Carol Kleinman,1 Zhibin Wu,1 Sayed Abdelwahab,1,{ddagger} Wuyuan Lu,1 and Alfredo Garzino-Demo1*

Division of Basic Science, Institute of Human Virology, University of Maryland Biotechnology Institute, 725 West Lombard Street, Baltimore, Maryland 21201,1 Center for Cancer Research Nanobiology Program, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702,2 Department of Maxillofacial Surgery, S. Giovanni Battista Hospital, University of Torino, Turin, Italy3

Received 14 July 2005/ Accepted 23 August 2005

ß-Defensins are small (3 to 5 kDa in size) secreted antimicrobial and antiviral proteins that are components of innate immunity. ß-Defensins are secreted by epithelial cells, and they are expressed at high levels in several mucosae, including the mouth, where the concentration of these proteins can reach 100 µg/ml. Because of these properties, we wondered whether they could be part of the defenses that lower oral transmission of human immunodeficiency virus (HIV) compared to other mucosal sites. Our data show that select ß-defensins, especially human ß-defensin 2 (hBD2) and hBD3, inhibit R5 and X4 HIV infection in a dose-dependent manner at doses that are compatible with or below those measured in the oral cavity. We observed that ß-defensin treatment inhibited accumulation of early products of reverse transcription, as detected by PCR. We could not, however, detect any reproducible inhibition of env-mediated fusion, and we did not observe any modulation of HIV coreceptors following treatment with hBD1 and hBD2, in both resting and phytohemagglutinin-activated cells. Our data instead suggest that, besides a direct inactivation of HIV virions, hBD2 inhibits HIV replication in the intracellular environment. Therefore, we speculate that ß-defensins mediate a novel antiretroviral mechanism that contributes to prevention of oral HIV transmission in the oral cavity. Immunohistochemical data on hBD2 expression in oral mucosal tissue shows that hBD2 is constitutively expressed, forming a barrier layer across the epithelium in healthy subjects, while in HIV-positive subjects levels of hBD2 expression are dramatically diminished. This may predispose HIV-positive subjects to increased incidence of oral complications associated with HIV infection.

* Corresponding author. Mailing address: Division of Basic Science, Institute of Human Virology, University of Maryland Biotechnology Institute, Room S613, 725 West Lombard Street, Baltimore, MD 21201. Phone: (410) 706-4689. Fax: (410) 706-4694. E-mail: garzinod{at}umbi.umd.edu.

{dagger} A.G.-D. and P.G.-D. dedicate this study to the loving memory of Maresa Molaschi and Mario Garzino.

§ Present address: Institute for Molecular Medicine and Infectious Diseases and Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129.

{ddagger} Present address: Department of Microbiology and Immunology, Faculty of Medicine, El-Minia University, El-Minia 61111, Egypt.

Journal of Virology, November 2005, p. 14318-14329, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.14318-14329.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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