Suppression of human papillomavirus gene expression in vitro and in vivo by herpes simplex virus type 2 infection

Virology. 2003 Sep 15;314(1):147-60. doi: 10.1016/s0042-6822(03)00440-9.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Down-Regulation*
  • Female
  • Gene Expression Regulation, Viral
  • Herpes Genitalis / complications*
  • Herpes Genitalis / virology
  • Herpesvirus 2, Human / pathogenicity*
  • Humans
  • Mice
  • Mice, Nude
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / metabolism
  • Papillomaviridae / genetics
  • Papillomaviridae / metabolism
  • Papillomaviridae / pathogenicity*
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / virology
  • Repressor Proteins*
  • Ribonucleases
  • Tissue Transplantation
  • Transplantation, Heterologous
  • Tumor Cells, Cultured
  • Vagina / virology
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*

Substances

  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Fusion
  • Oncogene Proteins, Viral
  • Repressor Proteins
  • Viral Proteins
  • virion host shutoff protein, Simplexvirus
  • Ribonucleases