Complete nucleotide sequence of a beta‐cell tropic variant of coxsackievirus B4

Abstract

A mouse pancreas-adapted variant of coxsackievirus B4 (P-CB4) has been shown to replicate in, and cause an excessive release of insulin from, 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 been shown to cause host cell protein synthesis shut-off in beta cells and 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 the 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.

Enterovirus RNA sequences in sera of schoolchildren in the general population and their association with type 1-diabetes-associated autoantibodies

“…Now the introduction of molecular approaches has opened up new possibilities to evaluate the role of viral infections, and some studies have indeed confirmed the preliminary hypothesis that a link exists between enteroviral infection and development of T1D (Clements et al, 1995; Andréoletti et al, 1997; Lönnrot et al, 2000a;Kawashima et al, 2004). Besides, it has been shown in vitro that coxsackievirus B4 can replicate in pancreatic beta cells and can cause an excessive release of insulin (Titchener et al, 1994). The E2 strain of human coxsackievirus B4 can induce a diabetic-like syndrome in a mouse model (Kang et al, 1994).…”

A New Look at Viruses in Type 1 Diabetes

“…They sequenced the entire genome of this variant and compared it with the nucleotide sequence of the prototype strain. They found only 7 amino acids that were different between the two strains [212]. The identification of critical sites (nucleotides or amino acids) responsible for the diabetogenicity of Coxsackie B4 virus remains to be determined.…”

The role of viruses in human diabetes

“…In the first of these studies [44] a coxsackie B4 variant which caused metabolic changes in islets, including human islets, was studied and its structure compared with the prototype CB4 virus. This variant had been passaged in pancreatic tissue and was mildly diabetic in mice.…”