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.

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The prevalence of herpes simplex virus (HSV) infection globally is high, and although there is no cure for it, the antiviral drug acyclovir is used to alleviate symptoms. There are two types of HSV: HSV-1, which typically infects the oral area, and HSV-2, which is associated with genital infections. A mother who carries the infection may transmit it to a neonate in different ways, most commonly via vaginal delivery in the presence of active lesions. There are three types of HSV disease that affect newborns: skin, eyes or mouth (SEM) disease, central nervous system (CNS) disease, or disseminated disease. The purpose of this study was to examine the long-term effects of the infection and the treatment used in neonates infected with HSV. Data collection consisted of original case reports published in Medline, CINHAL, and Google Scholar. Two case reports were found, and this narrative review compares the cases, which report recurrences and outcomes of HSV infection identified in the three databases. Both cases were consistent with recurrence of CNS disease, and one showed signs of a slight developmental delay that may have been related to the CNS insult.

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Much research is being conducted into the causes of human cancer. A number of human autosomal recessive diseases such as Xeroderma Pigmentosum are characterized at least in part by a defect or aberration in one or more forms of DNA repair and at the same time an elevated incidence of cancer. Also, carcinogens cause mutations in DNA and the greater the carcinogenicity, the greater the mutagenicity. As a result, much attention has been focused on DNA repair and its relationship to cancer incidence. The HCR of V antigen formation by UV-irradiated Adenovirus type 2 (Ad 2) was examined using apparently normal human fibroblasts, tumor cells (HeLa CCL2), and cells transformed by Ad 5 DNA (293, 293 N3S). A decrease in the HCR of V antigen formation was found for HeLa CCL2 cells as compared to apparently normal human fibroblasts, but not for the transformed cells. These results are discussed in terms of the characteristics of the cell types. Herpes simplex virus type I encodes a polymerase and thymidine kinase (tk) activity which are involved in viral DNA synthesis. Paa ᷇ 5, an HSV-1 mutant containing one or more mutations in the polymerase gene is an antimutator. If these are also involved in viral DNA repair, then the HSV-1 polymerase, tk activity, and mutant polymerases conferring altered mutation rates should provide excellent tools with which to probe cellular DNA repair processes and mutagenesis. The study of the HCR of plaque forming ability of HSV-1 KOS wild type (WT), Paa ᷇ 5 and PTK3B (lacking thymidine kinase activity ) using VERO cells revealed a decrease in the HCR of Paa ᷇ 5 and increase of surviving fractions of PTK3B with respect to that of HSV-1 KOS WT. Similar studies using apparently normal human fibroblasts, Xeroderma Pigmentosum and Cockayne Syndrome cells also implicated the HSV-1 polymerase in viral DNA repair. The results are discussed in terms of the function of the HSV-1 polymerase and the DNA repair abilities of XP and CS cells. / Thesis / Master of Science (MSc)