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ARS Home » Research » Publications at this Location » Publication #66315
Title: RETROVIRAL INSERTIONAL ACTIVATION IN A HERPESVIRUS: TRANSCRIPTIONAL ACTIVATION OF US GENES BY AN INTEGRATED LTR IN A MAREK'S DISEASE VIRUS CLONE

Author
item JONES, DAN - CASE WESTERN RESERVE
item Witter, Richard
item KUNG, HSING-JIEN - CASE WESTERN RESERVE

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/20/1996
Publication Date: N/A
Citation: N/A

Interpretive Summary: Marek's disease (MD) is an important viral disease of chickens. The MD virus contains over 70 genes that determine its various functions but little is known about which gene controls which function. Virus with mutations in specific genes would be useful to determine gene function but such viruses have been difficult to create. One mutant MD virus was found with an inserted gene from another type of virus. This study describes th structure of the mutant and shows that the inserted gene induces several adjacent genes to produce RNA transcripts. Since the ability of the virus to induce disease is markedly reduced, this mutation may identify regions of the virus associated with disease induction.

Technical Abstract: Insertional activation of host protooncogenes has been recognized as a basic mechanism by which nonacute retrovirus induces cancers. Our previous work has demonstrated that retrovirus can efficiently integrate into DNA virus genome. Specifically, coinfection of cultured fibroblasts with a chicken herpesvirus, Marek's disease virus (MDV), and a chicken retrovirus results in frequent stable retroviral insertions into the herpes virus genome. Such insertions could potentially alter the gene expressions and possible phenotypes of the herpesvirus. In this paper, we report the characterization of a replication-competent clone of MDV with integrated retroviral sequences. This virus was isolated from a chicken following injection of fibroblasts that were coinfected with MDV and the retrovirus, reticuloendotheliosis virus (REV). Transcripts originating from the authentic REV LTR promoters were obtained that encode adjoining MDV genes, SORF2, US1 and US10. This virus replicates well in culture but has an unusual phenotype in chickens with attenuated virulence producing no nerve lesions but severe thymic atrophy. While the causal relationship of this insertion and the observed phenotypes remains to be established, our data provides the first evidence of retroviral insertional activation of herpes virus genes.