Human beta-defensins suppress human immunodeficiency virus infection: potential role in mucosal protection.
Beta-defensins are small (3 to 5 kDa in size) secreted antimicrobial and antiviral proteins that are components of innate immunity. Beta-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 microg/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 beta-defensins, especially human beta-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 beta-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 beta-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.
Sun
Lingling
L
Division of Basic Science, Institute of Human Virology, University of Maryland Biotechnology Institute, Room S613, 725 West Lombard Street, Baltimore, MD 21201, USA. garzinod@umbi.umd.edu.
Finnegan
Catherine M
CM
Kish-Catalone
Tina
T
Blumenthal
Robert
R
Garzino-Demo
Paolo
P
La Terra Maggiore
Gian M
GM
Berrone
Sid
S
Kleinman
Carol
C
Wu
Zhibin
Z
Abdelwahab
Sayed
S
Lu
Wuyuan
W
Garzino-Demo
Alfredo
A
D002459:Cell Fusion; D002460:Cell Line; D002478:Cells, Cultured; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D008214:Lymphocytes / Q000821:virology; D016133:Polymerase Chain Reaction; D023083:beta-Defensins / Q000502:physiology*
D023083:beta-Defensins