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Genetic and antigenic analyses of a Puumala virus isolate as a potential vaccine strain

机译:普马拉病毒分离株作为潜在疫苗株的遗传和抗原分析

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Puumala virus (PUUV), a causative agent of hemorrhagic fever with renal syndrome (HFRS), is prevalent in Europe and European Russia. No vaccine has been developed for PUUV-associated HFRS, primarily because of the low viral yield in cultured cells. A PUUV strain known as DTK/Ufa-97 was isolated in Russia and adapted for growth in Vero E6 cells maintained in serum-free medium. The DTK/Ufa-97 strain produced a higher viral titer in serum-free medium, suggesting that it may prove useful in the development of an HFRS vaccine. When PUUV-infected Vero E6 cells were grown in serum-free medium, the DTK/Ufa-97 strain yielded more copies of intracellular viral RNA and a higher viral titer in the culture fluid than did the Sotkamo strain. Phylogenetic analysis revealed that PUUVs can be classified into multiple lineages according to geographical origin, and that the DTK/Ufa-97 strain is a member of the Bashkiria-Saratov lineage. The deduced amino acid sequences of the small, medium, and large segments of the DTK/Ufa-97 strain were 99.2% to 100%, 99.3% to 99.8%, and 99.8% identical, respectively, to those of the Bashkirian PUUV strains and 96.9%, 92.6%, and 97.4% identical, respectively, to those of the Sotkamo strain, indicating that the PUUVs are genetically diverse. However, DTK/Ufa-97 and other strains of PUUV exhibited similar patterns of binding to a panel of monoclonal antibodies against Hantaan virus. In addition, diluted antisera (i.e., ranging from 1:160 to 1:640) specific to three strains of PUUV neutralized both homologous and heterologous viruses. These results suggest that the DTK/Ufa-97 strain is capable of extensive growth and is antigenically similar to genetically distant strains of PUUV.
机译:Puumala病毒(PUUV)是肾综合征出血热(HFRS)的病原体,在欧洲和欧洲的俄罗斯很普遍。尚未开发出用于PUUV相关的HFRS的疫苗,这主要是因为培养细胞的病毒产量低。在俄罗斯分离出一种称为DTK / Ufa-97的PUUV菌株,该菌株适于在无血清培养基中维持的Vero E6细胞中生长。 DTK / Ufa-97菌株在无血清培养基中产生了更高的病毒滴度,表明它可能被证明可用于开发HFRS疫苗。当PUUV感染的Vero E6细胞在无血清培养基中生长时,与Sotkamo菌株相比,DTK / Ufa-97菌株在培养液中可产生更多的细胞内病毒RNA拷贝,并具有更高的病毒滴度。系统发育分析表明,PUUVs可以根据地理起源分为多个谱系,并且DTK / Ufa-97菌株是Bashkiria-Saratov谱系的成员。 DTK / Ufa-97菌株的小片段,中片段和大片段的推导氨基酸序列分别与Bashkirian PUUV菌株和Bashkirian PUUV菌株的氨基酸序列相同,分别为99.2%至100%,99.3%至99.8%和99.8%。与Sotkamo菌株的同源性分别为96.9%,92.6%和97.4%,这表明PUUV具有遗传多样性。然而,DTK / Ufa-97和其他PUUV菌株显示出与一组抗汉坦病毒的单克隆抗体结合的相似模式。另外,对三种PUUV毒株特异的稀释的抗血清(即,在1:160至1:640的范围内)中和了同源和异源病毒。这些结果表明,DTK / Ufa-97菌株能够广泛生长,并且在抗原上类似于PUUV在遗传上相距遥远的菌株。

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