Suppression of human papillomavirus gene expression in vitro and in vivo by herpes simplex virus type 2 infection.
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.
D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D015967:Gene Expression Regulation, Viral; D006558:Herpes Genitalis / Q000150:complications* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism; D027383:Papillomaviridae / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology; D012097:Repressor Proteins; D012260:Ribonucleases; D016378:Tissue Transplantation; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014621:Vagina / Q000821:virology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
C068651:E6 protein, Human papillomavirus type 16; D015514:Oncogene Proteins, Fusion; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D014764:Viral Proteins; C070722:virion host shutoff protein, Simplexvirus; D012260:Ribonucleases