Human herpesvirus-8 (Kaposi's sarcoma-associated herpesvirus) ORF50 interacts synergistically with the tat gene product in transactivating the human immunodeficiency virus type 1 LTR.
Human herpesvirus-8 (HHV-8) is a lymphotropic virus associated with several AIDS-related neoplasms. Two ORFs play a critical role in the regulation of virus replication: ORF50, encoding an immediate-early transcriptional activator, and ORF57, encoding a post-transcriptional regulator. We analysed their effects on the activation of the human immunodeficiency virus type 1 (HIV-1) LTR. ORF50 interacted synergically with tat, inducing a 10-fold enhancement of HIV-1 LTR transactivation. This effect occurred both in BCBL-1 cells, latently infected with HHV-8, and in HL3T1 cells, an epithelial cell line non-permissive to HHV-8 infection. Also, ORF57 enhanced tat-induced transactivation of HIV-1 LTR, but only in BCBL-1 cells, suggesting that its action was likely mediated by the induction of other viral functions. Finally, when both ORFs were expressed, the enhancement of transactivation induced by ORF50 was partially inhibited. The findings suggest that ORF57 can modulate ORF50 activity and that ORF50 may render biologically active small amounts of tat.
Caselli
Elisabetta
E
Department of Experimental & Diagnostic Medicine, Section of Microbiology, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy1.
Menegazzi
Paola
P
Department of Experimental & Diagnostic Medicine, Section of Microbiology, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy1.
Bracci
Arianna
A
Department of Experimental & Diagnostic Medicine, Section of Microbiology, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy1.
Galvan
Monica
M
Department of Experimental & Diagnostic Medicine, Section of Microbiology, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy1.
Cassai
Enzo
E
Department of Experimental & Diagnostic Medicine, Section of Microbiology, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy1.
Di Luca
Dario
D
Department of Experimental & Diagnostic Medicine, Section of Microbiology, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy1.
D002460:Cell Line; D015696:Gene Products, tat / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D019288:Herpesvirus 8, Human / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016366:Open Reading Frames / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014775:Virus Activation; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus