Mayberry Colleen L, Nelson Christian D S, Maginnis Melissa S
Department of Molecular and Biomedical Sciences, The University of Maine, Orono, ME, USA.
Biological Sciences Department, SUNY Cortland, Cortland, NY, USA.
Curr Clin Microbiol Rep. 2017 Sep;4(3):132-141. doi: 10.1007/s40588-017-0069-3. Epub 2017 Aug 1.
JC polyomavirus (JCPyV) is a significant human pathogen that causes an asymptomatic infection in the kidney in the majority of the population. In immunosuppressed individuals, the virus can become reactivated and spread to the brain, causing the fatal, demyelinating disease progressive multifocal leukoencephalopathy (PML). There are currently limited treatment options for this fatal disease. Attachment to receptors and entry into host cells are the initiating events in JCPyV infection and therefore an attractive target for therapeutics to prevent or treat PML. This review provides the current understanding of JCPyV attachment and entry events and the potential therapeutics to target these areas.
JCPyV attachment and entry to host cells is mediated by α2,6-linked lactoseries tetrasaccharide c (LSTc) and 5-hydroxytryptamine receptors (5-HTRs), respectively, and subsequent trafficking to the endoplasmic reticulum is required for infection. Recently, vaccines, monoclonal antibodies, and small molecules have shown promise as anti-viral and PML therapies.
This review summarizes our current understanding of JCPyV attachment, entry, and trafficking and the development of potential PML therapeutics that inhibit these critical steps in JCPyV infection.
JC多瘤病毒(JCPyV)是一种重要的人类病原体,在大多数人群中可引起肾脏无症状感染。在免疫抑制个体中,该病毒可重新激活并扩散至脑部,导致致命的脱髓鞘疾病——进行性多灶性白质脑病(PML)。目前针对这种致命疾病的治疗选择有限。病毒与受体结合并进入宿主细胞是JCPyV感染的起始事件,因此是预防或治疗PML的有吸引力的治疗靶点。本综述阐述了目前对JCPyV结合与进入事件的理解以及针对这些环节的潜在治疗方法。
JCPyV与宿主细胞的结合和进入分别由α2,6连接的乳糖系列四糖c(LSTc)和5-羟色胺受体(5-HTRs)介导,随后感染需要转运至内质网。最近,疫苗、单克隆抗体和小分子已显示出作为抗病毒和治疗PML疗法的潜力。
本综述总结了我们目前对JCPyV结合、进入和转运的理解,以及抑制JCPyV感染这些关键步骤的潜在PML治疗方法的进展。