title: Herpes simplex virus co-infection-induced Chlamydia trachomatis persistence is not mediated by any known persistence inducer or anti-chlamydial pathway.
abstract: Several inducers of chlamydial persistence have been described, including interferon-gamma (IFN-gamma), IFN-alpha, IFN-beta, and tumour necrosis factor-alpha (TNF-alpha) exposure, and iron, amino acid or glucose deprivation. A tissue-culture model of Chlamydia trachomatis/herpes simplex virus type-2 (HSV-2) co-infection indicates that viral co-infection stimulates the formation of persistent chlamydiae. This study was designed to ascertain whether co-infection-induced persistence is mediated by a previously characterized mechanism. Luminex assays indicate that IFN-gamma, IFN-alpha, and TNF-alpha are not released from co-infected cells. Semiquantitative RT-PCR studies demonstrate that IFN-beta, IFN-gamma, indoleamine 2,3-dioxygenase, lymphotoxin-alpha and inducible nitric oxide synthase are not expressed during co-infection. These data indicate that viral-induced persistence is not stimulated by any persistence-associated cytokine. Supplementation of co-infected cells with excess amino acids, iron-saturated holotransferrin, glucose or a combination of amino acids and iron does not restore chlamydial infectivity, demonstrating that HSV-2-induced persistence is not mediated by depletion of these nutrients. Finally, inclusions within co-infected cells continue to enlarge and incorporate C(6)-NBD-ceramide, indicating that HSV-2 co-infection does not inhibit vesicular transport to the developing inclusion. Collectively these data demonstrate that co-infection-induced persistence is not mediated by any currently characterized persistence inducer or anti-chlamydial pathway. Previous studies indicate that HSV-2 attachment and/or entry into the host cell is sufficient for stimulating chlamydial persistence, suggesting that viral attachment and/or entry may trigger a novel host pathway which restricts chlamydial development.
authors.affiliation: Department of Microbiology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614-0579, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Vanover
authors.affiliation: Department of Microbiology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614-0579, USA.
authors.forename: Jingru
authors.initials: J
authors.lastname: Sun
authors.affiliation: ViroMed Laboratories, Minnetonka, MN, USA.
authors.forename: Srilekha
authors.initials: S
authors.lastname: Deka
authors.affiliation: Department of Microbiology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614-0579, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kintner
authors.affiliation: Department of Pharmacology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Duffourc
authors.affiliation: Department of Microbiology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614-0579, USA.
authors.forename: Robert V
authors.initials: RV
authors.lastname: Schoborg
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D002460:Cell Line; D002692:Chlamydia trachomatis / Q000254:growth & development* / Q000472:pathogenicity; D020869:Gene Expression Profiling; D018258:Herpesvirus 2, Human / Q000254:growth & development*; D006801:Humans; D002479:Inclusion Bodies / Q000382:microbiology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis; D016898:Interferon-alpha / Q000378:metabolism; D016899:Interferon-beta / Q000096:biosynthesis; D007371:Interferon-gamma / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014774:Virulence / Q000187:drug effects
chemical_list: D000596:Amino Acids; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016898:Interferon-alpha; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; D007371:Interferon-gamma; D007501:Iron; D052247:Nitric Oxide Synthase Type II