Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
Localization and characterization of transforming regions in human cytomegalovirus and human herpesvirus 6.
Diss Abstr Int [B]; 53(7):3300 1993. Unique Identifier : AIDSLINE ICDB/93690162 Thompson JT; Georgetown Univ. Medical Center
Abstract:
Human herpesviruses have been associated with the etiology of several human cancers. The role these viruses play in carcinogenesis has not been delineated. To elucidate the role of human herpesviruses in carcinogenesis, in vitro model systems have been developed which have identified multiple DNA fragments capable of transforming cells. This thesis focused on identifying and characterizing the transforming potential of cloned DNA fragments from both human cytomegalovirus (HCMV) and human herpesvirus type 6 (HHV-6). HCMV strain Towne morphological transforming region II (mtrII) has been identified to a 3.0-kbp XbaI-BamHI DNA fragment which was retained in transformed cells. The transforming activity was localized to a 980-bp BanII-XhoI subfragment containing both promoter/regulatory elements as well as three open reading frames (ORFs) of 79-, 83-, and 34-amino acids (aa). In this thesis, both the promoter elements and the ORFs have been evaluated for transformation potential in rodent cells. Two promoter regions within mtrII have been identified and the mRNA start sites mapped. Through these analyses, HCMV mtrII was localized to the 79-aa ORF. Definitive proof that the 79-aa ORF encodes a transforming peptide was provided by insertional mutagenesis with translation termination linkers. This has provided the first demonstration of an HCMV transforming peptide. To identify transforming regions in HHV-6, a series of SalI clones have been analyzed for transforming potential. A 4.1-kbp SalI-L fragment was identified which exhibited transforming activity. This fragment was retained in focal and tumor-derived cell lines. In addition, the SalI-L fragment was shown to transactivate the HIV-1 LTR. Initial experiments have co-localized both the transforming and transactivating activities to a 1.9-kbp SalI-L-SH fragment and implicate a 283-aa ORF as the functional element. The identification of the 79-aa transforming peptide has allowed a better approach to determine the role of HCMV in human cancer. Moreover, the identification of a transforming and transactivating region in HHV-6 has strengthened the association of HHV-6 as a cofactor in AIDS and AIDS-related malignancies. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD92-36649.)
Keywords: Animal Cell Transformation, Neoplastic/*GENETICS Cytomegalovirus/*GENETICS Genes, Viral Herpesvirus 6, Human/*GENETICS Human Mutagenesis, Insertional Neoplasms/GENETICS/MICROBIOLOGY Open Reading Frames Promoter Regions (Genetics) Regulatory Sequences, Nucleic Acid Rodentia Terminator Regions (Genetics) THESIS 930630
M9361082
AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
