WALLEYE RETROVIRUSES ASSOCIATED WITH SKIN TUMORS AND HYPERPLASIAS ENCODE CYCLIN-D HOMOLOGS

Walleye dermal sarcoma (WDS) and walleye epidermal hyperplasia (WEH) a re skin diseases of walleye fish that appear and regress on a seasonal basis. We report here that the complex retroviruses etiologically ass ociated with WDS (WDS virus [WDSV]) and WEH (WEH viruses 1 and 2 [WEHV 1 and WEHV2, respectively]) encode D-type cyclin homologs, The retrovi ral cyclins (rv-cyclins) are distantly related to one another and to k nown cyclins and are not closely related to any walleye cellular gene based on low-stringency Southern blotting. Since aberrant expression o f D-type cyclins occurs in many human tumors, we suggest that expressi on 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, WEH V2, and WDSV are the first examples of retroviruses that encode cyclin homologs. WEH and WDS and their associated retroviruses represent a n ovel paradigm of retroviral tumor induction and, importantly, tumor re gression.