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 infection-mediated 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.

痘病毒是一种大型的DNA病毒，其蛋白衣壳被一个或多个脂质包膜包围。嵌入到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体与靶细胞的结合。尽管已经在体外研究了这些蛋白的功能，但在痘病毒病发病机理中它们的具体作用仍不清楚。在这里，我们目前的数据表明，假定软骨素从leporipoxvirus粘液瘤病毒结合蛋白M083易受感染期间显著毒力因子Oryctolagus兔子。去除M083导致病毒传播到区域淋巴结外的能力降低，并完全消除了感染介导的死亡率。体外因此，去除M083仅导致较小的细胞内复制缺陷，但是引起粘液瘤病毒从感染的上皮细胞扩散到原代淋巴细胞上的能力显着降低。我们假设，M083的生理作用因此是介导粘液瘤病毒在兔淋巴细胞上的传播，从而使这些细胞在整个感染兔中传播病毒。

重要事项痘病毒既代表一类人类病原体，又代表治疗人类恶性肿瘤的潜在治疗剂。因此，以多种方式了解这些药物的基本生物学对人类健康具有重要意义。虽然介导痘病毒结合的机制已在体外进行了充分研究，但这些机制如何影响体内痘病毒的发病机理仍不清楚。当前的研究通过证明推定的软骨素结合蛋白M083在易感性Oryctolagus粘液瘤病毒的发病过程中起着关键作用，进一步提高了我们对痘病毒结合如何影响病毒发病机理的理解。 通过改变病毒粒子转移到原代脾细胞上来影响病毒的传播。