Human herpesvirus 6 infects cervical epithelial cells and transactivates human papillomavirus gene expression.
To examine whether human herpesvirus 6 (HHV-6) is capable of infecting human cervical epithelial cells and altering expression of human papillomavirus (HPV) genes, HPV-immortalized or -transformed carcinoma cell lines were infected with HHV-6 variant A. No cytopathic effect was observed in infected cervical cells. However, immunofluorescence indicated that infected cells expressed early-late proteins of HHV-6 by day 3 postinfection. HHV-6 DNA was also detected by Southern blot hybridization after infection and persisted through continued subculture in an episomal state as proven by Gardella gel electrophoresis and fluorescence in situ hybridization. HHV-6 infection enhanced expression of HPV RNAs encoding the viral oncoproteins E6 and E7. Transient transfection assays showed that two HHV-6 molecular clones, pZVB-70 and pZVH-14, upregulated transcription 9- to 15-fold from a receptor plasmid containing the HPV type 18 regulatory sequences which control transcription in vivo. Cervical carcinoma cells infected with HHV-6 induced more rapid development of tumors in mice than did noninfected cells. These results are the first evidence that human cervical epithelial cells can be infected with HHV-6 and that HHV-6 contains transactivators which stimulate the HPV-transforming genes.
Chen
M
M
Laboratory of Biology, National Cancer Institute, Bethesda, Maryland 20892.
Popescu
N
N
Woodworth
C
C
Berneman
Z
Z
Corbellino
M
M
Lusso
P
P
Ablashi
D V
DV
DiPaolo
J A
JA
D000818:Animals; D002277:Carcinoma / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D004268:DNA-Binding Proteins; D004848:Epithelium / Q000821:virology; D005260:Female; D005455:Fluorescent Antibody Technique; D015654:Herpesvirus 6, Human / Q000235:genetics*; D006801:Humans; D051379:Mice; D009374:Neoplasms, Experimental; D009856:Oncogene Proteins, Viral / Q000032:analysis; D027383:Papillomaviridae / Q000235:genetics*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000821:virology*
D004279:DNA, Viral; D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; C062495:oncogene protein E7, Human papillomavirus type 6