Simian hemorrhagic fever virus: Recent advances.
Simian hemorrhagic fever virus: Recent advances.
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DOI：
10.1016/j.virusres.2014.11.024
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发表时间：
2015-04-16
期刊：
影响因子：
5
通讯作者：
Vatter HA
中科院分区：
文献类型：
--
作者：
Brinton MA;Di H;Vatter HA
SHFV在猕猴中诱导出血热，但在非洲非人灵长类动物中不诱导。SHFV感染猕猴细胞而不是狒狒细胞会诱导促炎细胞因子。独特的N-和C-末端基因编码SHFV的功能进行了分析。PLP 1 γ可以在上游位点以及预期的下游位点切割。感染性病毒产生需要八种次要结构蛋白。猴出血热病毒（Simian Hemorrhagic Fever Virus，SHFV）基因组与动脉炎病毒科其他成员基因组的不同之处在于，SHFV基因组5′端编码3个木瓜蛋白酶样蛋白酶（PLP 1 α、PLP 1 β和PLP 1 γ），3′端编码2组相邻的4个结构蛋白。预测了每个SHFV PLP 1的催化Cys和His残基和切割位点，并在用野生型或突变型多蛋白构建体进行的体外转录/翻译反应中测试了它们的功能。选定的自体蛋白水解产物的质谱分析确认切割位点的位置。PLP 1 α的催化Cys与Ala而不是Typ相邻是不寻常的。PLP 1 γ在下游和上游位点裂解。在体外转录/翻译反应中检测到中间体前体和替代切割产物，但在用SHFV nsp 1蛋白特异性抗体感染的MA 104细胞裂解物中仅检测到三种成熟的nsp 1蛋白。预测SHFV次要结构蛋白的重复组在功能上是冗余的。构建了一个稳定的全长感染性SHFV-LVR cDNA克隆，并产生了一组突变感染性克隆，每个克隆的一个次要结构蛋白的起始密码子突变。发现所有八种次要结构蛋白都是产生感染性细胞外病毒所需的。SHFV在猕猴中引起致命的出血热，但在天然宿主如狒狒中引起无症状的持续感染。在狒狒和猕猴的巨噬细胞和骨髓树突状细胞中比较了SHFV感染。猕猴细胞的病毒产量高于狒狒细胞。来自两种类型动物的巨噬细胞培养物在感染细胞的百分比方面存在显著差异。相比之下，相似比例的骨髓树突状细胞被感染，但病毒复制在猕猴细胞中是有效的，但在狒狒细胞中是无效的。SHFV感染可诱导猕猴细胞产生促炎细胞因子，包括IL-1β、IL-6、IL-12/23（p40）、TNF-α和MIP-1α，但对狒狒细胞无影响。
SHFV induces hemorrhagic fever in macaques but not in African nonhuman primates. SHFV infection of macaque but not baboon cells induces proinflammatory cytokines. Unique N- and C-terminal genes encoded by SHFV were functionally analyzed. PLP1γ can cleave at upstream sites as well as at the expected downstream site. Eight minor structural proteins are required for infectious virus production. The simian hemorrhagic fever virus (SHFV) genome differs from those of other members of the family Arteriviridae in encoding three papain-like one proteases (PLP1α, PLP1β and PLP1γ) at the 5′ end and two adjacent sets of four minor structural proteins at the 3′ end. The catalytic Cys and His residues and cleavage sites for each of the SHFV PLP1s were predicted and their functionality was tested in in vitro transcription/translation reactions done with wildtype or mutant polyprotein constructs. Mass spectrometry analyses of selected autoproteolytic products confirmed cleavage site locations. The catalytic Cys of PLP1α is unusual in being adjacent to an Ala instead of a Typ. PLP1γ cleaves at both downstream and upstream sites. Intermediate precursor and alternative cleavage products were detected in the in vitro transcription/translation reactions but only the three mature nsp1 proteins were detected in SHFV-infected MA104 cell lysates with SHFV nsp1 protein-specific antibodies. The duplicated sets of SHFV minor structural proteins were predicted to be functionally redundant. A stable, full-length, infectious SHFV-LVR cDNA clone was constructed and a set of mutant infectious clones was generated each with the start codon of one of the minor structural proteins mutated. All eight of the minor structural proteins were found to be required for production of infectious extracellular virus. SHFV causes a fatal hemorrhagic fever in macaques but asymptomatic, persistent infections in natural hosts such as baboons. SHFV infections were compared in macrophages and myeloid dendritic cells from baboons and macaques. Virus yields were higher from macaque cells than from baboon cells. Macrophage cultures from the two types of animals differed dramatically in the percentage of cells infected. In contrast, similar percentages of myeloid dendritic cells were infected but virus replication was efficient in the macaque cells but inefficient in the baboon cells. SHFV infection induced the production of pro-inflammatory cytokines, including IL-1β, IL-6, IL-12/23(p40), TNF-α and MIP-1α, in macaque cells but not baboon cells.
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影响因子：
5.4
作者：
Hwang, YK;Brinton, MA
通讯作者：
Brinton, MA
影响因子：
3.7
作者：
Lee C;Yoo D
通讯作者：
Yoo D
影响因子：
5
作者：
Fang Y;Snijder EJ
通讯作者：
Snijder EJ
影响因子：
3.7
作者：
Bailey AL;Lauck M;Weiler A;Sibley SD;Dinis JM;Bergman Z;Nelson CW;Correll M;Gleicher M;Hyeroba D;Tumukunde A;Weny G;Chapman C;Kuhn JH;Hughes AL;Friedrich TC;Goldberg TL;O'Connor DH
通讯作者：
O'Connor DH
影响因子：
5
作者：
Maines, TR;Young, M;Brinton, MA
通讯作者：
Brinton, MA