Herpes Simplex Virus Glycoprotein D/Host Cell Surface Interaction Stimulates Chlamydia trachomatis Persistence via a Novel Pathway.

Vanover, Jennifer

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East Tennessee State University

Herpes Simplex Virus Glycoprotein D/Host Cell Surface Interaction Stimulates Chlamydia trachomatis Persistence via a Novel Pathway.

dc:creator Vanover, Jennifer

thesis:degree_name PhD (Doctor of Philosophy)

dc:date.issued2008

Abstract

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When presented with certain unfavorable environmental conditions, C. trachomatis reticulate bodies (RBs) enter into a viable, yet noncultivable state called persistence. Two hallmarks of persistent chlamydiae are swollen, aberrantly shaped RBs, as viewed by transmission electron microscopy and a decrease in infectious progeny. Several models of chlamydial persistence have been described, including interferon-γ (IFN-γ), IFN-α, IFN-β, and tumor necrosis factor-α-exposure and nutrient deprivation. Previously, we established an in vitro co-infection model of two of the most common sexually transmitted pathogens in the United States, C. trachomatis and Herpes Simplex Virus-2 (HSV). Data from this tissue culture model indicate that: i) viral co-infection stimulates the formation of persistent chlamydiae and ii) productive HSV replication is not required for persistence induction. Further studies indicate that, co-infection-induced persistence is not mediated by: i) any known anti-chlamydial cytokine; ii) activation of inducible nitric oxide synthase or indoleamine 2, 3-dioxygenase; iii) inhibition of vesicular trafficking or sphingomyelin transport to the inclusion or; iv) amino acid, iron or glucose deprivation. These data demonstrate that co-infection-induced persistence is mediated by a previously undescribed, novel mechanism. During long-term co-infection with UV-inactivated HSV-2, chlamydiae recover following an initial suppression of chlamydial infectivity. These data indicate that HSV-induced persistence, like other persistence models, is reversible. Co-incubation of fixed, HSV-2-infected inducer cells with viable, C. trachomatis infected responder cells suppresses production of infectious chlamydial progeny and stimulates the formation of swollen, aberrantly shaped RBs. Antibody neutralization of HSV glycoprotein D (gD), which prevents viral attachment to one of four known HSV co-receptors on the host cell surface, also prevents co-infection-induced persistence, suggesting that HSV gD interaction with host cell surface receptors can provide the necessary stimulus to alter C. trachomatis development. Finally, exposure of C. trachomatis infected cells to soluble, recombinant HSV-2 gD:Fc fusion proteins decreases production of infectious EBs to a similar degree observed in co-infected cultures. Thus, we hypothesize that interaction of HSV gD with the host cell surface triggers a novel host anti-chlamydial pathway that restricts chlamydial development.

Degree

thesis:*

Name thesis:degree_name: PhD (Doctor of Philosophy)
Level thesis:degree_level: Dissertation - unrestricted
Discipline thesis:degree_discipline: Biomedical Sciences
Year dc:date.issued: 2008

Author and committee

dc:creator, dc:contributor.*

Author dc:creator: Vanover, Jennifer

Subjects

dc:subject × 7

Rights

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Statement dc:rights: Copyright by the authors.

Identifiers

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Repository record dc:identifier: https://dc.etsu.edu/etd/2019
OAI identifier oai:identifier: oai:dc.etsu.edu:etd-3371

Herpes Simplex Virus Glycoprotein D/Host Cell Surface Interaction Stimulates <em>Chlamydia trachomatis</em> Persistence via a Novel Pathway.