Bae Y S, Eun H M, Pon R T, Giron D, Yoon J W
Department of Microbiology and Infectious Diseases, Julia McFarlane Diabetes Research Centre, University of Calgary, Alberta, Canada.
J Gen Virol. 1990 Mar;71 ( Pt 3):639-45. doi: 10.1099/0022-1317-71-3-639.
The diabetogenic D variant of encephalomyocarditis virus (EMC-D) was previously shown to differ from the non-diabetogenic B variant (EMC-B) by 14 nucleotides out of 7829 bases. Similar approaches with a new nondiabetogenic variant, EMC-DV1, obtained by plaque purification of the EMC-D variant stock pool, enabled us to narrow down further the possible genomic area responsible for the diabetogenicity of EMC virus. EMC-DV1 does not induce interferon in vitro, differing from the highly interferon-inducing EMC-B. The complete nucleotide sequence of EMC-DV1 was determined by RNA-dependent DNA sequencing and cDNA sequencing. The genomic size and organization of EMC-DV1 are similar to those of EMC-D and EMC-B, with a long open reading frame encoding a polyprotein of 2292 amino acids. Comparative analyses of sequence information as well as biological activities of EMC-DV1 with EMC-D and EMC-B suggest that (i) the diabetogenicity is apparently distinct from the ability to induce interferon, which is probably due to the single U base insertion at position 765 in EMC-B, and (ii) the diabetogenicity of EMC virus is most probably controlled by one or both of two amino acids, Phe 16 (on the leader peptide) and Ala 776 (152nd amino acid on the VP1) on the polyprotein.
先前研究表明，脑心肌炎病毒的致糖尿病D变体（EMC-D）与非致糖尿病B变体（EMC-B）在7829个碱基中有14个核苷酸不同。通过对EMC-D变体储备库进行噬斑纯化获得了一种新的非致糖尿病变体EMC-DV1，并采用类似方法，使我们能够进一步缩小可能与脑心肌炎病毒致糖尿病性相关的基因组区域。EMC-DV1在体外不诱导干扰素，这与高度诱导干扰素的EMC-B不同。通过RNA依赖性DNA测序和cDNA测序确定了EMC-DV1的完整核苷酸序列。EMC-DV1的基因组大小和结构与EMC-D和EMC-B相似，具有一个长开放阅读框，编码一个由2292个氨基酸组成的多蛋白。对EMC-DV1与EMC-D和EMC-B的序列信息以及生物学活性进行比较分析表明：（i）致糖尿病性显然与诱导干扰素的能力不同，这可能是由于EMC-B中第765位的单个U碱基插入；（ii）脑心肌炎病毒的致糖尿病性很可能由多蛋白上的两个氨基酸之一或两者控制，即前导肽上的苯丙氨酸16和VP1上的丙氨酸776（第152个氨基酸）。
