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      Herpes Simplex Virus Type 1 Penetrates the Basement Membrane in Human Nasal Respiratory Mucosa

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          Herpes simplex virus infections are highly prevalent in humans. However, the current therapeutics suffer important drawbacks such as limited results in neonates, increasing occurrence of resistance and impeded treatment of stromal infections. Remarkably, interactions of herpesviruses with human mucosa, the locus of infection, remain poorly understood and the underlying mechanisms in stromal infection remain controversial.

          Methodology/Principal Findings

          A human model consisting of nasal respiratory mucosa explants was characterised. Viability and integrity were examined during 96 h of cultivation. HSV1-mucosa interactions were analysed. In particular, we investigated whether HSV1 is able to reach the stroma.

          Explant viability and integrity remained preserved. HSV1 induced rounding up and loosening of epithelial cells with very few apoptotic and necrotic cells observed. Following 16–24 h of infection, HSV1 penetrated the basement membrane and replicated in the underlying lamina propria.


          This human explant model can be used to study virus-mucosa interactions and viral mucosal invasion mechanisms. Using this model, our results provide a novel insight into the HSV1 stromal invasion mechanism and for the first time directly demonstrate that HSV1 can penetrate the basement membrane.

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          Most cited references 64

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          Differential requirement for caspase 9 in apoptotic pathways in vivo.

          Mutation of Caspase 9 (Casp9) results in embryonic lethality and defective brain development associated with decreased apoptosis. Casp9-/- embryonic stem cells and embryonic fibroblasts are resistant to several apoptotic stimuli, including UV and gamma irradiation. Casp9-/- thymocytes are also resistant to dexamethasone- and gamma irradiation-induced apoptosis, but are surprisingly sensitive to apoptosis induced by UV irradiation or anti-CD95. Resistance to apoptosis is accompanied by retention of the mitochondrial membrane potential in mutant cells. In addition, cytochrome c is translocated to the cytosol of Casp9-/- ES cells upon UV stimulation, suggesting that Casp9 acts downstream of cytochrome c. Caspase processing is inhibited in Casp9-/- ES cells but not in thymocytes or splenocytes. Comparison of the requirement for Casp9 and Casp3 in different apoptotic settings indicates the existence of at least four different apoptotic pathways in mammalian cells.
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            Herpes simplex virus type 2 in the United States, 1976 to 1994.

            Herpes simplex virus type 2 (HSV-2) infection is usually transmitted sexually and can cause recurrent, painful genital ulcers. In neonates the infection is potentially lethal. We investigated the seroprevalence and correlates of HSV-2 infection in the United States and identified changes in HSV-2 seroprevalence since the late 1970s. Serum samples and questionnaire data were collected during the National Health and Nutrition Examination Surveys (NHANES) II (1976 to 1980) and III (1988 to 1994). HSV-2 antibody was assessed with an immunodot assay specific for glycoprotein gG-2 of HSV-2. From 1988 to 1994, the seroprevalence of HSV-2 in persons 12 years of age or older in the United States was 21.9 percent (95 percent confidence interval, 20.2 to 23.6 percent), corresponding to 45 million infected people in the noninstitutionalized civilian population. The seroprevalence was higher among women (25.6 percent) than men (17.8 percent) and higher among blacks (45.9 percent) than whites (17.6 percent). Less than 10 percent of all those who were seropositive reported a history of genital herpes infection. In a multivariate model, the independent predictors of HSV-2 seropositivity were female sex, black race or Mexican-American ethnic background, older age, less education, poverty, cocaine use, and a greater lifetime number of sexual partners. As compared with the period from 1976 to 1980, the age-adjusted seroprevalence of HSV-2 rose 30 percent (95 percent confidence interval, 15.8 to 45.8 percent). The seroprevalence quintupled among white teenagers and doubled among whites in their twenties. Among blacks and older whites, the increases were smaller. Since the late 1970s, the prevalence of HSV-2 infection has increased by 30 percent, and HSV-2 is now detectable in roughly one of five persons 12 years of age or older nationwide. Improvements in the prevention of HSV-2 infection are needed, particularly since genital ulcers may facilitate the transmission of the human immunodeficiency virus.
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              Herpes simplex viruses.


                Author and article information

                Role: Editor
                PLoS One
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                15 July 2011
                : 6
                : 7
                [1 ]Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
                [2 ]Department of Otorhinolaryngology, University Hospital Ghent, Ghent, Belgium
                [3 ]Laboratory of Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
                [4 ]Department of Morphology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
                [5 ]Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
                [6 ]Tibotec BVBA, Beerse, Belgium
                University of Minnesota, United States of America
                Author notes

                Conceived and designed the experiments: SG HWF HJN. Performed the experiments: SG APV LS AR JG SC. Analyzed the data: SG CB HWF WVdB RFC HJN. Wrote the paper: SG.

                Glorieux et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                Page count
                Pages: 10
                Research Article
                Viral Transmission and Infection
                Viral Entry
                Host-Pathogen Interaction
                Molecular Cell Biology
                Extracellular Matrix
                Basement Membrane
                Clinical Research Design
                Infectious Diseases
                Viral Diseases
                Herpes Simplex
                Infectious Disease Modeling
                Nasal Diseases
                Respiratory Infections
                Upper Respiratory Tract Infections



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