The HIV-1 tat protein enhances E2-dependent human papillomavirus 16 transcription.
Epidemiologic studies show an association between infection with human immunodeficiency virus type 1 (HIV-1) and human papillomavirus (HPV) associated anogenital disease. To investigate possible molecular mechanisms of HIV-1 modulation of HPV expression, we studied the effect of an HIV-1 regulatory protein, tat1, on gene expression directed by the upstream regulatory region (URR) of HPV type 16 (HPV 16). HPV 16 URR-directed chloramphenicol acetyltransferase (CAT) expression driven by the native HPV 16 promoter (P97) was increased in the presence of tat1 alone. Tat1 also reversed E2-mediated repression of P97-directed CAT expression. E2 mediated CAT expression with URR constructs containing the SV40 promoter was enhanced when tat1 and E2 were cotransfected. Using a cervical carcinoma cell line (SiHa), E2 enhancement of URR-directed gene expression was elevated in the presence of extracellular tat1 or during cocultivation with HIV-1-infected cells. These results show HIV can modulate HPV gene expression in cell culture and that the increased rate of HPV-associated cervical disease in asymptomatic HIV-seropositive women may result from HPV-HIV molecular interactions.
Division of Viral and Rickettsial Diseases, Centers for Disease Control, Atlanta, GA 30333.
S D
SD
Vernon
C E
CE
Hart
W C
WC
Reeves
J P
JP
Icenogle
D017088:AIDS-Related Opportunistic Infections / Q000150:complications; D002460:Cell Line; D004268:DNA-Binding Proteins; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015696:Gene Products, tat / Q000235:genetics* / Q000494:pharmacology; D015658:HIV Infections / Q000150:complications; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation; D014162:Transfection; D014412:Tumor Virus Infections / Q000150:complications; D002583:Uterine Cervical Neoplasms / Q000150:complications; D054322:tat Gene Products, Human Immunodeficiency Virus
D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D015696:Gene Products, tat; D009856:Oncogene Proteins, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus