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J. Virol., Sep 1995, 5320-5331, Vol 69, No. 9
DL Holzschu, D Martineau, SK Fodor, VM Vogt, PR Bowser and JW Casey
Walleye dermal sarcoma virus (WDSV) is a fish retrovirus associated with
the development of tumors in walleyes. We have determined the complete
nucleotide sequence of a DNA clone of WDSV, the N-terminal amino acid
sequences of the major proteins, and the start site for transcription. The
long terminal repeat is 590 bp in length, with the U3 region containing
consensus sequences likely to be involved in viral gene expression. A
predicted histidyl-tRNA binding site is located 3 nucleotides distal to the
3' end of the long terminal repeat. Virus particles purified by isopycnic
sedimentation followed by rate zonal sedimentation showed major
polypeptides with molecular sizes of 90, 25, 20, 14, and 10 kDa. N-terminal
sequencing of these allowed unambiguous assignment of the small
polypeptides as products of the gag gene, including CA and NC, and the
large polypeptide as the TM product of env. The 582-amino-acid (aa) Gag
protein precursor is predicted to be myristylated as is found for most
retroviruses. NC contains a single Cys-His motif like those found in all
retroviruses except spumaviruses. The WDSV pro and pol genes are in the
same translational reading frame as gag and thus apparently are translated
after termination suppression. The env gene encodes a surface (SU) protein
of 469 aa predicted to be highly glycosylated and a large transmembrane
(TM) protein of 754 aa. The sequence of TM is unusual in that it ends in a
very hydrophobic segment of 65 residues containing a single charged
residue. Following the env gene are two nonoverlapping long open reading
frames of 290 aa (orf-A) and 306 aa (orf-B), neither of which shows
significant sequence similarity with known genes. A third open reading
frame of 119 aa (orf-C) is located in the leader region preceding gag. The
predicted amino acid sequence of reverse transcriptase would place WDSV
phylogenetically closest to the murine leukemia virus-related genus of
retroviruses. However, other members of this genus do not have accessory
genes, suggesting that WDSV acquired orf-A, orf-B, and perhaps orf-C late
in its evolution. We hypothesize by analogy with other complex retroviruses
that the accessory genes of WDSV function in the regulation of
transcription and in RNA processing and also in the induction of walleye
dermal sarcoma.
Copyright © 1995, American Society for Microbiology
Nucleotide sequence and protein analysis of a complex piscine retrovirus, walleye dermal sarcoma virus
Department of Microbiology, Parasitology and Immunology, Cornell University, Ithaca, New York 14853, USA.
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