Glycosaminoglycan binding by arboviruses: a cautionary tale.
Glycosaminoglycan binding by arboviruses: a cautionary tale.
复制标题
DOI：
10.1099/jgv.0.001726
复制
发表时间：
2022-02-01
期刊：
影响因子：
--
通讯作者：
Klimstra, William B
中科院分区：
文献类型：
--
作者：
Alcorn, Maria D H;Klimstra, William B
虫媒病毒是医学上重要的节肢动物传播的病毒，可引起人类一系列疾病，从发热性疾病到关节炎、脑炎和出血热。考虑到它们的传播周期，这些病毒面临着在进化上不同的生物体中复制的挑战，这些生物体可以包括蜱虫、苍蝇、蚊子、鸟类、啮齿动物、爬行动物和灵长类动物。此外，它们的细胞附着受体利用可能受到在脊椎动物中产生高和持续的血清病毒血症的相反需要的影响，使得在吸血节肢动物血液餐期间有效地收集病毒颗粒，但它们还必须充分结合到不同生物体上的细胞结构，使得可以启动生产性感染并产生病毒血症。糖胺聚糖（GAG）基团的硫酸化多糖，主要是硫酸乙酰肝素（HS），已被鉴定为许多虫媒病毒的细胞附着部分。最初将GAG结合鉴定为虫媒病毒的一种表型，似乎涉及仅由于病毒分离株适应细胞培养物中生长而产生的该属性。然而，最近，至少一种虫媒病毒（东部马脑炎）的自然循环毒株已显示有效结合HS，并且在已发表的研究中GAG结合表型继续与虫媒病毒感染相关。如果GAG是许多自然循环虫媒病毒的附着受体，这可能导致通过阻断病毒-GAG相互作用开发广谱抗病毒疗法。本文综述了GAG/HS结合作为自然循环虫媒病毒株的表型的现有数据，强调在分离过程中避免组织培养扩增和人为表型的重要性。
Arboviruses are medically important arthropod-borne viruses that cause a range of diseases in humans from febrile illness to arthritis, encephalitis and hemorrhagic fever. Given their transmission cycles, these viruses face the challenge of replicating in evolutionarily divergent organisms that can include ticks, flies, mosquitoes, birds, rodents, reptiles and primates. Furthermore, their cell attachment receptor utilization may be affected by the opposing needs for generating high and sustained serum viremia in vertebrates such that virus particles are efficiently collected during a hematophagous arthropod blood meal but they must also bind sufficiently to cellular structures on divergent organisms such that productive infection can be initiated and viremia generated. Sulfated polysaccharides of the glycosaminoglycan (GAG) groups, primarily heparan sulfate (HS), have been identified as cell attachment moieties for many arboviruses. Original identification of GAG binding as a phenotype of arboviruses appeared to involve this attribute arising solely as a consequence of adaptation of virus isolates to growth in cell culture. However, more recently, naturally circulating strains of at least one arbovirus, eastern equine encephalitis, have been shown to bind HS efficiently and the GAG binding phenotype continues to be associated with arbovirus infection in published studies. If GAGs are attachment receptors for many naturally circulating arboviruses, this could lead to development of broad-spectrum antiviral therapies through blocking of the virus-GAG interaction. This review summarizes the available data for GAG/HS binding as a phenotype of naturally circulating arbovirus strains emphasizing the importance of avoiding tissue culture amplification and artifactual phenotypes during their isolation.