Griffithsin protects mice from genital herpes by preventing cell-to-cell spread

Briana Nixon, Martha Stefanidou, Pedro M M Mesquita, Esra Fakioglu, Theodore Segarra, Lisa Rohan, William Halford, Kenneth E. Palmer, Betsy Herold

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Griffithsin, which binds N-linked glycans on gp120 to prevent HIV entry, has the most potent HIV-1 inhibitory activity described for any antiviral lectin and is being developed for topical preexposure prophylaxis. The current studies were designed to further assess its potential by exploring its activity against herpes simplex virus 2 (HSV-2), a cofactor for HIV acquisition, in vitro and in a murine model. Safety was evaluated by examining its impact on epithelial barrier integrity in polarized cultures and testing whether repeated intravaginal dosing potentiates the susceptibility of mice to genital herpes. Griffithsin displayed modest inhibitory activity against HSV-2 if present during viral entry but completely blocked plaque formation if present postentry, reduced plaque size, and prevented cell-to-cell spread. These in vitro findings translated to significant protection against genital herpes in mice treated with 0.1% griffithsin gel. Griffithsin, but not placebo gel, prevented viral spread (visualized with a luciferase-expressing virus), significantly reduced disease scores, and resulted in greater survival (P<0.05, log rank test). Protection persisted when HSV-2 was introduced in seminal plasma. Although griffithsin triggered a small decline in transepithelial electrical resistance in polarized cultures, this did not translate to any significant increase in the ability of HIV to migrate from the apical to the basolateral chamber nor to an increase in susceptibility to HSV-2 in mice treated with griffithsin gel for 7 days. These findings demonstrate that griffithsin inhibits HSV-2 by a unique mechanism of blocking cell-to-cell spread and support its further development for HIV and HSV-2 prevention.

Original languageEnglish (US)
Pages (from-to)6257-6269
Number of pages13
JournalJournal of Virology
Volume87
Issue number11
DOIs
StatePublished - Jun 2013

Fingerprint

Human herpesvirus 2
Herpes Genitalis
Human Herpesvirus 2
genitalia
mice
HIV
Gels
gels
cells
electrical resistance
seminal plasma
luciferase
Human immunodeficiency virus 1
Semen
Luciferases
Electric Impedance
Cell Size
Lectins
lectins
placebos

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Nixon, B., Stefanidou, M., Mesquita, P. M. M., Fakioglu, E., Segarra, T., Rohan, L., ... Herold, B. (2013). Griffithsin protects mice from genital herpes by preventing cell-to-cell spread. Journal of Virology, 87(11), 6257-6269. https://doi.org/10.1128/JVI.00012-13

Griffithsin protects mice from genital herpes by preventing cell-to-cell spread. / Nixon, Briana; Stefanidou, Martha; Mesquita, Pedro M M; Fakioglu, Esra; Segarra, Theodore; Rohan, Lisa; Halford, William; Palmer, Kenneth E.; Herold, Betsy.

In: Journal of Virology, Vol. 87, No. 11, 06.2013, p. 6257-6269.

Research output: Contribution to journalArticle

Nixon, B, Stefanidou, M, Mesquita, PMM, Fakioglu, E, Segarra, T, Rohan, L, Halford, W, Palmer, KE & Herold, B 2013, 'Griffithsin protects mice from genital herpes by preventing cell-to-cell spread', Journal of Virology, vol. 87, no. 11, pp. 6257-6269. https://doi.org/10.1128/JVI.00012-13
Nixon B, Stefanidou M, Mesquita PMM, Fakioglu E, Segarra T, Rohan L et al. Griffithsin protects mice from genital herpes by preventing cell-to-cell spread. Journal of Virology. 2013 Jun;87(11):6257-6269. https://doi.org/10.1128/JVI.00012-13
Nixon, Briana ; Stefanidou, Martha ; Mesquita, Pedro M M ; Fakioglu, Esra ; Segarra, Theodore ; Rohan, Lisa ; Halford, William ; Palmer, Kenneth E. ; Herold, Betsy. / Griffithsin protects mice from genital herpes by preventing cell-to-cell spread. In: Journal of Virology. 2013 ; Vol. 87, No. 11. pp. 6257-6269.
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