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Walleye retroviruses associated with skin tumors and hyperplasias encode cyclin D homologs.

ABSTRACT: Walleye dermal sarcoma (WDS) and walleye epidermal hyperplasia (WEH) are skin diseases of walleye fish that appear and regress on a seasonal basis. We report here that the complex retroviruses etiologically associated with WDS (WDS virus [WDSV]) and WEH (WEH viruses 1 and 2 [WEHV1 and WEHV2, respectively]) encode D-type cyclin homologs. The retroviral cyclins (rv-cyclins) are distantly related to one another and to known cyclins and are not closely related to any walleye cellular gene based on low-stringency Southern blotting. Since aberrant expression of D-type cyclins occurs in many human tumors, we suggest that expression of the rv-cyclins may contribute to the development of WDS or WEH. In support of this hypothesis, we show that rv-cyclin transcripts are made in developing WDS and WEH and that the rv-cyclin of WDSV induces cell cycle progression in yeast (Saccharomyces cerevisiae). WEHV1, WEHV2, and WDSV are the first examples of retroviruses that encode cyclin homologs. WEH and WDS and their associated retroviruses represent a novel paradigm of retroviral tumor induction and, importantly, tumor regression.

SUBMITTER: LaPierre LA

PROVIDER: S-EPMC110292 | biostudies-literature | 1998 Nov

REPOSITORIES: biostudies-literature

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Walleye retroviruses associated with skin tumors and hyperplasias encode cyclin D homologs.

LaPierre L A LA Casey J W JW Holzschu D L DL

Journal of virology 19981101 11

Walleye dermal sarcoma (WDS) and walleye epidermal hyperplasia (WEH) are skin diseases of walleye fish that appear and regress on a seasonal basis. We report here that the complex retroviruses etiologically associated with WDS (WDS virus [WDSV]) and WEH (WEH viruses 1 and 2 [WEHV1 and WEHV2, respectively]) encode D-type cyclin homologs. The retroviral cyclins (rv-cyclins) are distantly related to one another and to known cyclins and are not closely related to any walleye cellular gene based on l ...[more]

PMID: 9765420

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Project description:Walleye epidermal hyperplasia virus types 1 and 2 (WEHV1 and WEHV2, respectively) are associated with a hyperproliferative skin lesion on walleyes that appears and regresses seasonally. We have determined the complete nucleotide sequences and transcriptional profiles of these viruses. WEHV1 and WEHV2 are large, complex retroviruses of 12,999 and 13,125 kb in length, respectively, that are closely related to one another and to walleye dermal sarcoma virus (WDSV). These walleye retroviruses contain three open reading frames, orfA, orfB, and orfC, in addition to gag, pol, and env. orfA and orfB are adjacent to one another and located downstream of env. The OrfA proteins were previously identified as cyclin D homologs that may contribute to the induction of cell proliferation leading to epidermal hyperplasia and dermal sarcoma. The sequence analysis of WEHV1 and WEHV2 revealed that the OrfB proteins are distantly related to the OrfA proteins, suggesting that orfB arose by gene duplication. Presuming that the precursor of orfA and orfB was derived from a cellular cyclin, these genes are the first accessory genes of complex retroviruses that can be traced to a cellular origin. WEHV1, WEHV2, and WDSV are the only retroviruses that have an open reading frame, orfC, of considerable size (ca. 130 amino acids) in the leader region preceding gag. While we were unable to predict a function for the OrfC proteins, they are more conserved than OrfA and OrfB, suggesting that they may be biologically important to the viruses. The transcriptional profiles of WEHV1 and WEHV2 were also similar to that of WDSV; Northern blot analyses detected only low levels of the orfA transcripts in developing lesions, whereas abundant levels of genomic, env, orfA, and orfB transcripts were detected in regressing lesions. The splice donors and acceptors of individual transcripts were identified by reverse transcriptase PCR. The similarities of WEHV1, WEHV2, and WDSV suggest that these viruses use similar strategies of viral replication and induce cell proliferation by a similar mechanism.

Dataset Information

Walleye retroviruses associated with skin tumors and hyperplasias encode cyclin D homologs.

Publications

Walleye retroviruses associated with skin tumors and hyperplasias encode cyclin D homologs.

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