Myxoma Virus M083 Is a Virulence Factor Which Mediates Systemic Dissemination
Myxoma Virus M083 Is a Virulence Factor Which Mediates Systemic Dissemination
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DOI：
10.1128/jvi.02186-17
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发表时间：
2018-04-01
影响因子：
5.4
通讯作者：
Bartee, E.
中科院分区：
文献类型：
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作者：
Wolfe, A. M.;Dunlap, K. M.;Bartee, E.
痘病毒是一种大型 DNA 病毒，其蛋白质衣壳被一个或多个脂质包膜包围。嵌入这些脂质包膜中的是三种保守的病毒蛋白，它们被认为介导病毒粒子与靶细胞的结合。虽然这些蛋白质的功能已在体外进行了研究，但它们在痘病毒疾病发病机制中的具体作用仍不清楚。在这里，我们提供的数据表明，来自麻风痘病毒粘液瘤病毒的假定软骨素结合蛋白 M083 在易感兔的感染过程中是一个重要的毒力因子。去除 M083 会降低病毒扩散到区域淋巴结以外的能力，并完全消除感染介导的死亡率。在体外，去除 M083 仅导致轻微的细胞内复制缺陷，但会导致粘液瘤病毒从受感染的上皮细胞扩散到初级淋巴细胞的能力显着降低。因此，我们假设 M083 的生理作用是介导粘液瘤病毒在兔淋巴细胞上的传播，使这些细胞能够在感染的兔体内传播病毒。 重要性 痘病毒代表一类人类病原体和治疗人类恶性肿瘤的潜在治疗剂。因此，了解这些药物的基本生物学对人类健康具有多方面的重要意义。虽然介导痘病毒结合的机制已在体外得到充分研究，但这些机制如何影响体内痘病毒发病机制仍不清楚。目前的研究通过证明假定的软骨素结合蛋白 M083 在易感家兔粘液瘤病毒的发病机制中发挥着关键作用，通过改变病毒粒子转移到原代脾细胞上来影响病毒传播，从而加深了我们对痘病毒结合如何影响病毒发病机制的理解。
Poxviruses are large, DNA viruses whose protein capsid is surrounded by one or more lipid envelopes. Embedded into these lipid envelopes are three conserved viral proteins which are thought to mediate binding of virions to target cells. While the function of these proteins has been studied in vitro, their specific roles during the pathogenesis of poxviral disease remain largely unclear. Here we present data demonstrating that the putative chondroitin binding protein M083 from the leporipoxvirus myxoma virus is a significant virulence factor during infection of susceptible Oryctolagus rabbits. Removal of M083 results in a reduced capacity of virus to spread beyond the regional lymph nodes and completely eliminates infectionmediated mortality. In vitro, removal of M083 results in only minor intracellular replication defects but causes a significant reduction in the ability of myxoma virus to spread from infected epithelial cells onto primary lymphocytes. We hypothesize that the physiological role of M083 is therefore to mediate the spread of myxoma virus onto rabbit lymphocytes, allowing these cells to disseminate virus throughout infected rabbits.IMPORTANCE Poxviruses represent both a class of human pathogens and potential therapeutic agents for the treatment of human malignancy. Understanding the basic biology of these agents is therefore significant to human health in a variety of ways. While the mechanisms mediating poxviral binding have been well studied in vitro, how these mechanisms impact poxviral pathogenesis in vivo remains unclear. The current study advances our understanding of how poxviral binding impacts viral pathogenesis by demonstrating that the putative chondroitin binding protein M083 plays a critical role during the pathogenesis of myxoma virus in susceptible Oryctolagus rabbits by impacting viral dissemination through changes in the transfer of virions onto primary splenocytes.