LaRue Rebecca, Myers Suzanne, Brewer Laurie, Shaw Daniel P, Brown Corrie, Seal Bruce S, Njenga M Kariuki
Department of Veterinary Pathobiology, University of Minnesota, St. Paul, Minnesota 55108, USA.
J Virol. 2003 Sep;77(17):9136-46. doi: 10.1128/jvi.77.17.9136-9146.2003.
Previous studies using wild-type Encephalomyocarditis virus (EMCV) and Mengo virus, which have long poly(C) tracts (61 to 146 C's) at the 5' nontranslated region of the genome, and variants of these viruses genetically engineered to truncate or substitute the poly(C) tracts have produced conflicting data on the role of the poly(C) tract in the virulence of these viruses. Analysis of the nucleotide sequence of an EMCV strain isolated from an aborted swine fetus (EMCV 30/87) revealed that the virus had a poly(C) tract that was 7- to 10-fold shorter than the poly(C) tracts of other EMCV strains and 4-fold shorter than that of Mengo virus. Subsequently, we investigated the virulence and pathogenesis of this naturally occurring short-poly(C)-tract-containing virus in rodents, pigs, and nonhuman primates. Infection of C57BL/6 mice, pigs, and cynomolgus macaques resulted in similar EMCV 30/87 pathogenesis, with the heart and brain as the primary sites of infections in all three animals, but with different disease phenotypes. Sixteen percent of EMCV 30/87-infected pigs developed acute fatal cardiac failure, whereas the rest of the pigs were overtly asymptomatic for as long as 90 days postinfection (p.i.), despite extensive myocardial and central nervous system (CNS) pathological changes. In contrast, mice infected with >/==" BORDER="0">4 PFU of EMCV 30/87 developed acute encephalitis that resulted in the death of all animals (n = 25) between days 2 and 7 p.i. EMCV 30/87-infected macaques remained overtly asymptomatic for 45 days, despite extensive myocardial and CNS pathological changes and viral persistence in more than 50% of the animals. The short poly(C) tract in EMCV 30/87 (CUC(5)UC(8)) was comparable to that of strain 2887A/91 (C(10)UCUC(3)UC(10)), another recent porcine isolate.
先前使用野生型脑心肌炎病毒（EMCV）和门戈病毒的研究表明，这些病毒在基因组的5'非翻译区有长的聚（C）序列（61至146个C），并且对这些病毒进行基因工程改造以截断或替代聚（C）序列的变体，就聚（C）序列在这些病毒毒力中的作用产生了相互矛盾的数据。对从流产猪胎儿分离的一株EMCV（EMCV 30/87）的核苷酸序列分析表明，该病毒的聚（C）序列比其他EMCV毒株的聚（C）序列短7至10倍，比门戈病毒的聚（C）序列短4倍。随后，我们研究了这种天然存在的含短聚（C）序列的病毒在啮齿动物、猪和非人类灵长类动物中的毒力和发病机制。C57BL/6小鼠、猪和食蟹猕猴感染后导致了相似的EMCV 30/87发病机制，心脏和大脑是所有三种动物的主要感染部位，但疾病表型不同。16%感染EMCV 30/87的猪发生急性致命性心力衰竭，而其余猪在感染后长达90天内明显无症状，尽管有广泛的心肌和中枢神经系统（CNS）病理变化。相比之下，感染>4 PFU EMCV 30/87的小鼠发生急性脑炎，导致所有动物（n = 25）在感染后第2至7天死亡。感染EMCV 30/87的猕猴在45天内明显无症状，尽管有广泛的心肌和CNS病理变化且超过50%的动物体内有病毒持续存在。EMCV 30/87中的短聚（C）序列（CUC(五)UC(八)）与另一株最近从猪分离的毒株2887A/91（C(十)UCUC(三)UC(十)）的聚（C）序列相当。
