COMPLETE NUCLEOTIDE-SEQUENCE OF A BETA-CELL TROPIC VARIANT OF COXSACKIEVIRUS-B4

A mouse pancreas-adapted variant of coxsackie-virus B4 (P-CB4) has bee n shown to replicate in, and cause an excessive release of insulin fro m, pancreatic beta cells cultured in vitro. The prototype CB4 strain ( JVB Benschoten), from which the adapted variant was derived, although able to replicate in cultured islets does not cause a similar release of insulin from the beta cells. The pancreas-adapted virus has also be en shown to cause host cell protein synthesis shut-off in beta cells a nd to inhibit (pro)insulin biosynthesis. These metabolic changes occur in the absence of cytolytic damage [Szopa et al.: Bioscience Reports 5:63-69, 1985 and Cell Biochemistry and Function 4:181-187, 1986]. To investigate the genetic basis for this beta cell tropism, the complete nucleotide sequence of P-CB4 has been determined and compared to that of the previously published sequence of the prototype CB4 strain (JVB Benschoten) [Jenkins et al.: Journal of General Virology 68:1835-1848 , 1987]. Twenty-five nucleotide sequence differences were observed. Of these, six occur in the 5' noncoding region of the genome and 19 in t he coding region (resulting in seven amino acid changes). The possible significance of these changes in relation to the beta cell tropism of the pancreas-adapted virus is discussed. (C) 1994 Wiley-Liss, Inc.