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钱德里普拉病毒分离株的全基因组与其他弹状病毒的比较分析。

Whole genomes of Chandipura virus isolates and comparative analysis with other rhabdoviruses.

机构信息

National Institute of Virology, Pashan, Pune, Maharashtra, India.

出版信息

PLoS One. 2012;7(1):e30315. doi: 10.1371/journal.pone.0030315. Epub 2012 Jan 17.

DOI:10.1371/journal.pone.0030315
PMID:22272333
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3260278/
Abstract

The Chandipura virus (CHPV) belonging to the Vesiculovirus genus and Rhabdoviridae family, has recently been associated with a number of encephalitis epidemics, with high mortality in children, in different parts of India. No full length genome sequences of CHPV isolates were available in GenBank and little is known about the molecular markers for pathogenesis. In the present study, we provide the complete genomic sequences of four isolates from epidemics during 2003-2007. These sequences along with the deduced sequence of the prototype isolate of 1965 were analysed using phylogeny, motif search, homology modeling and epitope prediction methods. Comparison with other rhaboviruses was also done for functional extrapolations. All CHPV isolates clustered with the Isfahan virus and maintained several functional motifs of other rhabdoviruses. A notable difference with the prototype vesiculovirus, Vesicular Stomatitis Virus was in the L-domain flanking sequences of the M protein that are known to be crucial for interaction with host proteins. With respect to the prototype isolate, significant additional mutations were acquired in the 2003-2007 isolates. Several mutations in G mapped onto probable antigenic sites. A mutation in N mapped onto regions crucial for N-N interaction and a putative T-cell epitope. A mutation in the Casein kinase II phosphorylation site in P may attribute to increased rates of phosphorylation. Gene junction comparison revealed changes in the M-G junction of all the epidemic isolates that may have implications on read-through and gene transcription levels. The study can form the basis for further experimental verification and provide additional insights into the virulence determinants of the CHPV.

摘要

钱德普拉病毒(CHPV)属于 Vesiculovirus 属和 Rhabdoviridae 科,最近与印度不同地区的一些脑炎流行有关,儿童死亡率很高。在 GenBank 中没有 CHPV 分离株的全长基因组序列,对发病机制的分子标记知之甚少。在本研究中,我们提供了 2003-2007 年流行期间的四个分离株的完整基因组序列。使用系统发育、基序搜索、同源建模和表位预测方法分析了这些序列以及 1965 年原型分离株的推导序列。还对其他 Rhabdoviruses 进行了比较,以进行功能外推。所有 CHPV 分离株与伊斯法罕病毒聚集在一起,并保持了其他 Rhabdoviruses 的几个功能基序。与原型 Vesiculovirus,水疱性口炎病毒的一个显著差异在于 M 蛋白的 L 结构域侧翼序列,这些序列已知对于与宿主蛋白相互作用至关重要。与原型分离株相比,2003-2007 年分离株中获得了显著的额外突变。在 G 中映射到可能的抗原位点的几个突变。在 N 中映射到对 N-N 相互作用和推定的 T 细胞表位至关重要的突变。P 中酪蛋白激酶 II 磷酸化位点的突变可能归因于磷酸化率的增加。基因接头比较显示所有流行分离株的 M-G 接头发生了变化,这可能对通读和基因转录水平产生影响。该研究可以为进一步的实验验证奠定基础,并为 CHPV 的毒力决定因素提供更多的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f47/3260278/66e84540e8b0/pone.0030315.g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f47/3260278/28752b896065/pone.0030315.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f47/3260278/c4943bb373b5/pone.0030315.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f47/3260278/8c73f3c4226e/pone.0030315.g003.jpg
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