Document 0540 DOCN M9460540 TI trans-activation of the HIV promoter by a cDNA and its genomic clones of human herpesvirus-6. DT 9404 AU Zhou Y; Chang CK; Qian G; Chandran B; Wood C; Department of Neurology and Microbiology, University of Miami; School of Medicine, Florida 33101. SO Virology. 1994 Mar;199(2):311-22. Unique Identifier : AIDSLINE MED/94167865 AB Human herpesvirus 6 (HHV-6) is a lymphotropic herpesvirus, and in vitro, it can productively infect human CD4+ T cells as HIV-1. Co-infection of T cells by HIV-1 and HHV-6 can lead to both activation of the HIV-1 promoter and acceleration of the cytopathic effects. An HHV-6 (GS) cDNA clone, pCD41, encoding for a 41-kDa nuclear protein was identified and characterized previously (Chang and Balachandran, J. Virol. 65, 2884-2894 and 7085, 1991). Sequence analyses show that this protein has significant homology with the human cytomegalovirus UL44 gene coding for the ICP36 family of early-late-class phosphoprotein. Using this cDNA as the probe, a 3.8-kb EcoRI genomic fragment encoding the HHV-6(GS)P41 was cloned and designated as pGD41. When cotransfected with the HIV LTR CAT into CV-1 cells, both the pCD41 and pGD41 clones trans-activated the HIV LTR. Sequence analyses of pCD41 indicate that there are two potential open reading frames (ORFs), A and B, which are homologous to the ORFs found in the genomic clone pGD41. Deletion constructs of the pCD41 clone demonstrated that ORF-A was critical for the HIV LTR activation. Deletion analyses of the pCD41 ORF-A and the use of promoter constructs further mapped an internal functional promoter within the pCD41 sequence that can direct the synthesis of the trans-activating protein. By using HIV LTR deletion mutants, the NF-kappa B binding sites were found to be critical for response to the pCD41 trans-activation. DE Amino Acid Sequence Animal Base Sequence Cell Line Cercopithecus aethiops Cloning, Molecular DNA, Complementary/GENETICS/*PHYSIOLOGY Gene Expression Regulation, Viral/PHYSIOLOGY Herpesvirus 6, Human/GENETICS/*PHYSIOLOGY Human HIV Long Terminal Repeat/*PHYSIOLOGY HIV-1 Molecular Sequence Data NF-kappa B/PHYSIOLOGY Open Reading Frames/PHYSIOLOGY Phosphoproteins/GENETICS Promoter Regions (Genetics)/GENETICS/PHYSIOLOGY Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. T-Lymphocytes Trans-Activation (Genetics)/GENETICS/*PHYSIOLOGY Viral Proteins/*GENETICS JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).