Elucidating the role of the complement control protein in monkeypox pathogenicity.
Elucidating the role of the complement control protein in monkeypox pathogenicity.
复制标题
阐明补体控制蛋白在猴子病原性中的作用。
DOI：
10.1371/journal.pone.0035086
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Olson VA
中科院分区：
文献类型：
--
作者：
Hudson PN;Self J;Weiss S;Braden Z;Xiao Y;Girgis NM;Emerson G;Hughes C;Sammons SA;Isaacs SN;Damon IK;Olson VA
猴痘病毒(MPXV)会导致人类患上一种类似天花的疾病。临床和流行病学研究提供了两个地理上不同的猴痘病毒分支：西非和刚果盆地之间存在致病性差异的证据。对这两个分支的菌株的基因组分析发现，到目前为止已经测序的毒力较低的西非分离株中存在∼10kbp缺失。一个缺失的开放阅读框架编码补体控制蛋白(CCP)的猴痘病毒同源物。这种调节蛋白阻止了补体激活的经典途径和替代途径的启动。在猴痘病毒中，CCP也被称为MOPICE，是一种∼24 kDa的分泌性蛋白，与这一超家族蛋白具有序列同源性。在这里，我们研究了CCP的表达及其在猴痘毒力和致病机制中的作用。Ccp被整合到西非菌株中，并通过同源重组从刚果盆地菌株中移除。野生型和重组猴痘病毒都证实了CCP的表达表型，并用C4b结合试验证实了CCP的活性。为了确定这种疾病的特征，对草原土拨鼠进行了鼻腔感染，并对疾病进展进行了30天的监测。从刚果盆地株中去除CCP降低了猴痘疾病的发病率和死亡率，但并没有显著降低病毒载量。在西非毒株中加入CCP可引起疾病表现的变化，但对与疾病相关的死亡率没有明显影响。这项研究确定CCP是猴痘发病机制中的一种重要的免疫调节蛋白，但并不是猴痘病毒刚果盆地分支中毒力增加的唯一原因。
Monkeypox virus (MPXV) causes a smallpox-like disease in humans. Clinical and epidemiological studies provide evidence of pathogenicity differences between two geographically distinct monkeypox virus clades: the West African and Congo Basin. Genomic analysis of strains from both clades identified a ∼10 kbp deletion in the less virulent West African isolates sequenced to date. One absent open reading frame encodes the monkeypox virus homologue of the complement control protein (CCP). This modulatory protein prevents the initiation of both the classical and alternative pathways of complement activation. In monkeypox virus, CCP, also known as MOPICE, is a ∼24 kDa secretory protein with sequence homology to this superfamily of proteins. Here we investigate CCP expression and its role in monkeypox virulence and pathogenesis. CCP was incorporated into the West African strain and removed from the Congo Basin strain by homologous recombination. CCP expression phenotypes were confirmed for both wild type and recombinant monkeypox viruses and CCP activity was confirmed using a C4b binding assay. To characterize the disease, prairie dogs were intranasally infected and disease progression was monitored for 30 days. Removal of CCP from the Congo Basin strain reduced monkeypox disease morbidity and mortality, but did not significantly decrease viral load. The inclusion of CCP in the West African strain produced changes in disease manifestation, but had no apparent effect on disease-associated mortality. This study identifies CCP as an important immuno-modulatory protein in monkeypox pathogenesis but not solely responsible for the increased virulence seen within the Congo Basin clade of monkeypox virus.
登录
查看更多内容
影响因子：
5.4
作者：
HRUBY, DE;GUARINO, LA;KATES, JR
通讯作者：
KATES, JR
影响因子：
5.4
作者：
BOONE, RF;ENSINGER, MJ;MOSS, B
通讯作者：
MOSS, B
影响因子：
56.9
作者：
KOTWAL, GJ;ISAACS, SN;MOSS, B
通讯作者：
MOSS, B
影响因子：
2.7
作者：
Chakrabarti, S;Sisler, JR;Moss, B
通讯作者：
Moss, B
影响因子：
3.8
作者：
Likos, AM;Sammons, SA;Damon, IK
通讯作者：
Damon, IK