θ Defensins Protect Cells from Infection by Herpes Simplex Virus by Inhibiting Viral Adhesion and Entry

Bushra Yasin, Wei Wang, Mabel Pang, Natalia V. Cheshenko, Teresa Hong, Alan J. Waring, Betsy Herold, Elizabeth A. Wagar, Robert I. Lehrer

Research output: Contribution to journalArticle

170 Citations (Scopus)

Abstract

We tested the ability of 20 synthetic θ defensins to protect cells from infection by type 1 and type 2 herpes simplex viruses (HSV-1 and -2, respectively). The peptides included rhesus θ defensins (RTDs) 1 to 3, originally isolated from rhesus macaque leukocytes, and three peptides (retrocyclins 1 to 3) whose sequences were inferred from human θ-defensin (DEFT) pseudogenes. We also tested 14 retrocyclin analogues, including the retro, enantio, and retroenantio forms of retrocyclin 1. Retrocyclins 1 and 2 and RTD 3 protected cervical epithelial cells from infection by both HSV serotypes, but only retrocyclin 2 did so without causing cytotoxicity or requiring preincubation with the virus. Surface plasmon resonance studies revealed that retrocyclin 2 bound to immobilized HSV-2 glycoprotein B (gB2) with high affinity (Kd, 13.3 nM) and that it did not bind to enzymatically deglycosylated gB2. Temperature shift experiments indicated that retrocyclin 2 and human α defensins human neutrophil peptide 1 (HNP 1) to HNP 3 protected human cells from HSV-2 by different mechanisms. Retrocyclin 2 blocked viral attachment, and its addition during the binding or penetration phases of HSV-2 infection markedly diminished nuclear translocation of VP16 and expression of ICP4. In contrast, HNPs 1 to 3 had little effect on binding but reduced both VP16 transport and ICP4 expression if added during the postbinding (penetration) period. We recently reported that θ defensins are miniature lectins that bind gp120 of human immunodeficiency virus type 1 (HIV-1) with high affinity and inhibit the entry of R5 and X4 isolates of HIV-1. Given its small size (18 residues), minimal cytotoxicity, lack of activity against vaginal lactobacilli, and effectiveness against both HSV-2 and HIV-1, retrocyclin 2 provides an intriguing prototype for future topical microbicide development.

Original languageEnglish (US)
Pages (from-to)5147-5156
Number of pages10
JournalJournal of Virology
Volume78
Issue number10
DOIs
StatePublished - May 2004
Externally publishedYes

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Defensins
herpes simplex
Simplexvirus
adhesion
Human immunodeficiency virus 1
viruses
Human Herpesvirus 2
peptides
Infection
infection
cytotoxicity
cells
Human herpesvirus 1
HIV-1
surface plasmon resonance
pseudogenes
Human Herpesvirus 1
Macaca mulatta
prototypes
lectins

ASJC Scopus subject areas

  • Immunology

Cite this

θ Defensins Protect Cells from Infection by Herpes Simplex Virus by Inhibiting Viral Adhesion and Entry. / Yasin, Bushra; Wang, Wei; Pang, Mabel; Cheshenko, Natalia V.; Hong, Teresa; Waring, Alan J.; Herold, Betsy; Wagar, Elizabeth A.; Lehrer, Robert I.

In: Journal of Virology, Vol. 78, No. 10, 05.2004, p. 5147-5156.

Research output: Contribution to journalArticle

Yasin, Bushra ; Wang, Wei ; Pang, Mabel ; Cheshenko, Natalia V. ; Hong, Teresa ; Waring, Alan J. ; Herold, Betsy ; Wagar, Elizabeth A. ; Lehrer, Robert I. / θ Defensins Protect Cells from Infection by Herpes Simplex Virus by Inhibiting Viral Adhesion and Entry. In: Journal of Virology. 2004 ; Vol. 78, No. 10. pp. 5147-5156.
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AU - Yasin, Bushra

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AU - Pang, Mabel

AU - Cheshenko, Natalia V.

AU - Hong, Teresa

AU - Waring, Alan J.

AU - Herold, Betsy

AU - Wagar, Elizabeth A.

AU - Lehrer, Robert I.

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