Truncated oncoproteins of retroviruses and hepatitis B virus: A lesson in contrasts

Minarovits, Janos and Niller, Hans Helmut (2019) Truncated oncoproteins of retroviruses and hepatitis B virus: A lesson in contrasts. INFECTION GENETICS AND EVOLUTION, 73. pp. 342-357. ISSN 1567-1348, 1567-7257

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Abstract

Members of the virus families Retroviridae and Hepadnaviridae use reverse transcriptase (RT) to synthesize a DNA copy of their genomic and pregenomic RNA, respectively, during the viral life cycle. A group of viruses belonging to Retroviridae ("acute transforming" retroviruses) as well as human hepatitis B virus (HBV), the prototype member of Hepadnaviridae (hepadnaviruses) are able to cause malignant neoplasms in infected hosts, due to the expression of pleiotropic "transforming proteins" encoded by the genomes of these reverse-transcribing tumor viruses. In this review we wish to compare the common and unique features of replication strategies characteristic of acute transforming retroviruses and HBV and summarize data related to the origin and evolution of their viral oncogenes either via transduction of cellular genes, or by accumulation of mutations in viral sequences that create a new open reading frame (overprinting). The exons of cellular genes (proto-onc genes or c-onc genes) incorporated into the genome of acute transforming retroviruses are regularly affected by deletions resulting in the expression of truncated viral oncoproteins which are frequently dysregulated compared to their cellular counterparts. These retroviral transforming proteins alter the behavior of their target cells (malignant transformation). HBx, a pleiotropic protein of HBV, regulates virus replication and contributes to hepatocarcinogenesis. In contrast to the v-onc genes of acute transforming retroviruses, the viral gene encoding the full-length, wild-type HBx (wtHBx) protein does not have a cellular counterpart. Mutations and deletions frequently affect, however, the HBV genome as well, resulting in the expression of truncated HBx proteins (trHBx) in liver cells. Truncated, especially C-terminal truncated variants of HBx (Ct-HBX proteins), may facilitate initiation and progression of liver carcinoma.

Item Type: Article
Uncontrolled Keywords: FELINE SARCOMA-VIRUS; AVIAN ERYTHROBLASTOSIS VIRUS; TRANSFORMING GENE-PRODUCT; MURINE LEUKEMIA-VIRUS; NUCLEOTIDE-SEQUENCE; X-PROTEIN; HEPATOCELLULAR-CARCINOMA; DNA INTEGRATION; REVERSE TRANSCRIPTION; HBX PROTEIN;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene
Depositing User: Petra Gürster
Date Deposited: 03 Apr 2020 07:08
Last Modified: 03 Apr 2020 07:08
URI: https://pred.uni-regensburg.de/id/eprint/26374

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