Human α- and β-defensins block multiple steps in herpes simplex virus infection

Ehsan Hazrati, Benjamin T. Galen, Wuyuan Lu, Wei Wang, Yan Ouyang, Marla J. Keller, Robert I. Lehrer, Betsy Herold

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)8658-8666
Number of pages9
JournalJournal of Immunology
Volume177
Issue number12
StatePublished - Dec 15 2006
Externally publishedYes

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Defensins
Virus Diseases
Simplexvirus
Heparitin Sulfate
Glycoproteins
Peptides
Viral Genes
Surface Plasmon Resonance
Anti-Infective Agents
Life Cycle Stages
Epithelial Cells
Gene Expression
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Human α- and β-defensins block multiple steps in herpes simplex virus infection. / Hazrati, Ehsan; Galen, Benjamin T.; Lu, Wuyuan; Wang, Wei; Ouyang, Yan; Keller, Marla J.; Lehrer, Robert I.; Herold, Betsy.

In: Journal of Immunology, Vol. 177, No. 12, 15.12.2006, p. 8658-8666.

Research output: Contribution to journalArticle

Hazrati, E, Galen, BT, Lu, W, Wang, W, Ouyang, Y, Keller, MJ, Lehrer, RI & Herold, B 2006, 'Human α- and β-defensins block multiple steps in herpes simplex virus infection', Journal of Immunology, vol. 177, no. 12, pp. 8658-8666.
Hazrati, Ehsan ; Galen, Benjamin T. ; Lu, Wuyuan ; Wang, Wei ; Ouyang, Yan ; Keller, Marla J. ; Lehrer, Robert I. ; Herold, Betsy. / Human α- and β-defensins block multiple steps in herpes simplex virus infection. In: Journal of Immunology. 2006 ; Vol. 177, No. 12. pp. 8658-8666.
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