Titchener P A, Jenkins O, Szopa T M, Taylor K W, Almond J W
Department of Microbiology, University of Reading Whiteknights, United Kingdom.
J Med Virol. 1994 Apr;42(4):369-73. doi: 10.1002/jmv.1890420408.
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.
柯萨奇病毒B4的小鼠胰腺适应性变体（P-CB4）已被证明可在体外培养的胰腺β细胞中复制，并导致胰岛素过度释放。适应性变体源自的原型CB4毒株（JVB Benschoten），虽然能够在培养的胰岛中复制，但不会导致β细胞释放类似的胰岛素。胰腺适应性病毒还被证明可导致β细胞中的宿主细胞蛋白质合成停止，并抑制（前体）胰岛素生物合成。这些代谢变化在不存在细胞溶解损伤的情况下发生[索帕等人：《生物科学报告》5：63 - 69，1985年；《细胞生物化学与功能》4：181 - 187，1986年]。为了研究这种β细胞嗜性的遗传基础，已确定了P-CB4的完整核苷酸序列，并与先前发表的原型CB4毒株（JVB Benschoten）的序列进行了比较[詹金斯等人：《普通病毒学杂志》68：1835 - 1848，1987年]。观察到25个核苷酸序列差异。其中，6个发生在基因组的5'非编码区，19个发生在编码区（导致7个氨基酸变化）。讨论了这些变化与胰腺适应性病毒的β细胞嗜性相关的可能意义。
