Abstract
Recent epidemiological studies have found that women infected with both herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) type 16 or HPV-18 are at greater risk of developing cervical carcinoma compared to women infected with only one virus. However, it remains unclear if HSV-2 is a cofactor for cervical cancer or if HPV and HSV-2 interact in any way. We have studied the effect of HSV-2 infection on HPV-11 gene expression in an in vitro double-infection assay. HPV transcripts were down-regulated in response to HSV-2 infection. Two HSV-2 vhs mutants failed to reduce HPV-16 E1;E4 transcripts. We also studied the effect of HSV-2 infection on preexisting experimental papillomas in a vaginal epithelial xenograft model. Doubly infected grafts demonstrated papillomatous transformation and the classical cytopathic effect from HSV-2 infection. HPV and HSV DNA signals were mutually exclusive. These studies may have therapeutic applications for HPV infections and related neoplasms.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Disease Models, Animal
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Down-Regulation*
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Female
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Gene Expression Regulation, Viral
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Herpes Genitalis / complications*
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Herpes Genitalis / virology
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Herpesvirus 2, Human / pathogenicity*
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Humans
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Mice
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Mice, Nude
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Oncogene Proteins, Fusion / genetics
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Oncogene Proteins, Fusion / metabolism
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Oncogene Proteins, Viral / genetics
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Oncogene Proteins, Viral / metabolism
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Papillomaviridae / genetics
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Papillomaviridae / metabolism
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Papillomaviridae / pathogenicity*
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Papillomavirus Infections / complications*
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Papillomavirus Infections / virology
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Repressor Proteins*
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Ribonucleases
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Tissue Transplantation
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Transplantation, Heterologous
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Tumor Cells, Cultured
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Vagina / virology
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Viral Proteins / genetics
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Viral Proteins / metabolism*
Substances
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E6 protein, Human papillomavirus type 16
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Oncogene Proteins, Fusion
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Oncogene Proteins, Viral
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Repressor Proteins
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Viral Proteins
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virion host shutoff protein, Simplexvirus
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Ribonucleases