TY - JOUR
T1 - Human α- and β-defensins block multiple steps in herpes simplex virus infection
AU - Hazrati, Ehsan
AU - Galen, Benjamin
AU - Lu, Wuyuan
AU - Wang, Wei
AU - Ouyang, Yan
AU - Keller, Marla J.
AU - Lehrer, Robert I.
AU - Herold, Betsy C.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2006/12/15
Y1 - 2006/12/15
N2 - This study examined the ability of nine human defensins (HD) to protect against herpes simplex virus infection. Noncytotoxic concentrations of all six α-defensins (HNP1-4, HD5, and HD6) and human β-defensin (hBD) 3 inhibited HSV infection. Two other β-defensins, hBD1 and 2, lacked this protective activity. Synchronized assays revealed that HNP-4, HD6, and hBD3 acted primarily by preventing binding and entry, whereas HNP1-3 and HD5 also inhibited postentry events. Even when added several hours after entry, substantial reduction in viral gene expression ensued. Human cervical epithelial cells incubated with HNP-1 or HD5 accumulated the peptides intracellularly. Surface plasmon resonance studies revealed that HNPs 1, 2, 3, and HD5 bound HSV glycoprotein B (gB) with high affinity, but showed minimal binding to heparan sulfate, the receptor for attachment. In contrast, HNP-4 and HD6 bound heparan sulfate, but not gB. HBD3 bound both gB and heparan sulfate, but hBD1 and hBD2 bound neither. Admixture of HD5 with hydroxyethylcellulose significantly protected mice from a viral challenge lethal to controls receiving an inactive peptide or hydroxyethylcellulose alone. These findings demonstrate that HDs act at multiple steps in the HSV life cycle and support the development of defensins or defensin-like peptides as microbicides.
AB - This study examined the ability of nine human defensins (HD) to protect against herpes simplex virus infection. Noncytotoxic concentrations of all six α-defensins (HNP1-4, HD5, and HD6) and human β-defensin (hBD) 3 inhibited HSV infection. Two other β-defensins, hBD1 and 2, lacked this protective activity. Synchronized assays revealed that HNP-4, HD6, and hBD3 acted primarily by preventing binding and entry, whereas HNP1-3 and HD5 also inhibited postentry events. Even when added several hours after entry, substantial reduction in viral gene expression ensued. Human cervical epithelial cells incubated with HNP-1 or HD5 accumulated the peptides intracellularly. Surface plasmon resonance studies revealed that HNPs 1, 2, 3, and HD5 bound HSV glycoprotein B (gB) with high affinity, but showed minimal binding to heparan sulfate, the receptor for attachment. In contrast, HNP-4 and HD6 bound heparan sulfate, but not gB. HBD3 bound both gB and heparan sulfate, but hBD1 and hBD2 bound neither. Admixture of HD5 with hydroxyethylcellulose significantly protected mice from a viral challenge lethal to controls receiving an inactive peptide or hydroxyethylcellulose alone. These findings demonstrate that HDs act at multiple steps in the HSV life cycle and support the development of defensins or defensin-like peptides as microbicides.
UR - http://www.scopus.com/inward/record.url?scp=33845401745&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33845401745&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.177.12.8658
DO - 10.4049/jimmunol.177.12.8658
M3 - Article
C2 - 17142766
AN - SCOPUS:33845401745
SN - 0022-1767
VL - 177
SP - 8658
EP - 8666
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -