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 papi llomavirus (HPV) genes, HPV-immortalized or -transformed carcinoma cel l lines were infected with HHV-6 variant A. No cytopathic effect was o bserved in infected cervical cells. However, immunofluorescence indica ted that infected cells expressed early-late proteins of HHV-6 by day 3 postinfection. HHV-6 DNA was also detected by Southern blot hybridiz ation after infection and persisted through continued subculture in an episomal state as proven by Gardella gel electrophoresis and fluoresc ence in situ hybridization. HHV-6 infection enhanced expression of HPV RNAs encoding the viral oncoproteins E6 and E7. Transient transfectio n assays showed that two HHV-6 molecular clones, pZVB-70 and pZVH-14, upregulated transcription 9- to 15-fold from a reporter plasmid contai ning the HPV type IS regulatory sequences which control transcription in vivo. Cervical carcinoma cells infected with HHV-6 induced more rap id development of tumors in mice than did noninfected cells. These res ults are the first evidence that human cervical epithelial cells can b e infected with HHV-6 and that HHV-6 contains transactivators which st imulate the HPV-transforming genes.