Tumorigenesis by human herpesvirus 8 vGPCR is accelerated by human immunodeficiency virus type 1 Tat.
Human herpesvirus 8 (HHV-8), also called Kaposi's sarcoma (KS) herpesvirus, can cause KS but is inefficient. Untreated human immunodeficiency virus type 1 (HIV-1) coinfection is a powerful risk factor. The HHV-8 chemokine receptor, vGPCR (ORF74), activates NF-kappaB and NF-AT, and their levels of activation are synergistically increased by HIV-1 Tat. Transgenic vGPCR mice develop KS-like tumors. A cell line derived from one such tumor expresses vGPCR and forms tumors in nude mice. Here we show that transfection of DNA encoding HIV-1 tat (but not a transactivation-defective mutant) into these tumor cells increases NF-kappaB and NF-AT activation levels and accelerates tumor formation. Tumorigenesis was also accelerated when Tat DNA was transfected into normal cells and the transfected cells were mixed with the tumor cells and injected into a single site. Tumorigenesis was also increased when the two cell types were injected at separate sites, suggesting that tumorigenesis is accelerated by Tat through soluble factors.
Institute of Human Virology, University of Maryland Biotechnology Institute, Baltimore, Maryland 21201, USA.
Hong-Guang
HG
Guo
Shibani
S
Pati
Mariola
M
Sadowska
Man
M
Charurat
Marvin
M
Reitz
D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D012514:Sarcoma, Kaposi / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D019076:Transgenes / Q000235:genetics; D054322:tat Gene Products, Human Immunodeficiency Virus
D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D004268:DNA-Binding Proteins; C115448:G protein-coupled receptor, Human herpesvirus 8; D015696:Gene Products, tat; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D019707:Receptors, Chemokine; D014157:Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt