PDF(Pubmed)
Abstract：
Recently, we identified the coxsackie and adenovirus receptor (CAR) as the entry receptor for rhesus enteric calicivirus (ReCV) isolate FT285 and demonstrated that co-expression of the CAR and the type B histo-blood group antigen (HBGA) is required to convert the resistant CHO cell line susceptible to infection. To address whether the CAR is also the functional entry receptor for other ReCV isolates and the requirement for specific HBGAs or other glycans, here we used a panel of recombinant CHO cell lines expressing the CAR and the type A, B, or H HBGAs alone or in combination. Infection studies with three diverse ReCV strains, the prototype GI.1 Tulane virus (TV), GI.2 ReCV-FT285, and GI.3 ReCV-FT7, identified that cell surface expression of the CAR is an absolute requirement for all three strains to promote susceptibility to infection, while the requirement for HBGAs varies among the strains. In addition to the CAR, ReCV-FT285 and TV require type A or B HBGAs for infection. In the absence of HBGAs, TV, but not Re-CV FT285, can also utilize sialic acids, while ReCV-FT7 infection is HBGA-independent and relies on CAR and sialic acid expression. In summary, we demonstrated strain-specific diversity of susceptibility requirements for ReCV infections and that CAR, type A and B HBGA, and sialic acid expression control susceptibility to infection with the three ReCV isolates studied. Our study also indicates that the correlation between in vitro HBGA binding and HBGAs required for infection is relatively high, but not absolute. This has direct implications for human noroviruses.IMPORTANCEHuman noroviruses (HuNoVs) are important enteric pathogens. The lack of a robust HuNoV cell culture system is a bottleneck for HuNoV cell culture-based studies. Often, cell culture-adapted caliciviruses that rapidly replicate in conventional cell lines and recapitulate biological features of HuNoVs are utilized as surrogates. Particularly, rhesus enteric caliciviruses (ReCVs) display remarkable similarities, including the primate host, clinical manifestation of gastroenteritis, genetic/antigenic diversity, and reliance on histo-blood group antigens (HBGAs) for attachment. While the HuNoV entry receptor(s) is unknown, the coxsackie and adenovirus receptor (CAR) has recently been identified as the ReCV entry receptor. Here, we identified the CAR, the type A and B HBGAs, and sialic acids as critical cell surface molecules controlling susceptibility to ReCV infections. The CAR is required for all ReCV isolates studied. However, the requirement for the different carbohydrate molecules varies among different ReCV strains. Our findings have direct implications for HuNoVs.
摘要：
最近,我们将柯萨奇和腺病毒受体(CAR)鉴定为恒河猴肠道杯状病毒(ReCV)分离株FT285的进入受体,并证明CAR和B型组织血型抗原(HBGA)的共表达是转化易感感染的耐药CHO细胞系所必需的.为了解决CAR是否也是其他ReCV分离株的功能进入受体以及对特定HBGA或其他聚糖的要求，在这里，我们使用了一组表达CAR和A型的重组CHO细胞系，B,或单独或组合使用HHBGA。使用三种不同的ReCV菌株进行感染研究，原型GI.1杜兰病毒（电视），GI.2ReCV-FT285和GI.3ReCV-FT7确定了CAR的细胞表面表达是所有三种菌株促进感染易感性的绝对必要条件。而HBA的需求因菌株而异。除了汽车,ReCV-FT285和TV需要A型或B型HBGA进行感染。在没有HBA的情况下，电视,但不是Re-CVFT285，也可以利用唾液酸，而ReCV-FT7感染不依赖HBGA，依赖于CAR和唾液酸表达。总之,我们证明了ReCV感染的敏感性要求的菌株特异性多样性，A型和B型HBGA，和唾液酸表达控制对研究的三种ReCV分离株感染的易感性。我们的研究还表明，体外HBGA结合和感染所需的HBGA之间的相关性相对较高，但不是绝对的。这对人类诺如病毒有直接影响。重要的人类诺如病毒（HuNoVs）是重要的肠道病原体。缺乏强大的HuNoV细胞培养系统是基于HuNoV细胞培养研究的瓶颈。通常,在常规细胞系中快速复制并概括HuNoV的生物学特征的适应细胞培养的杯状病毒被用作替代物。特别是,恒河猴肠道杯状病毒（ReCV）表现出显著的相似性，包括灵长类宿主,胃肠炎的临床表现，遗传/抗原多样性，并依赖组织血型抗原（HBGA）进行附着。虽然HuNoV进入受体是未知的，柯萨奇和腺病毒受体(CAR)最近被鉴定为ReCV进入受体.这里,我们确认了这辆车,A型和B型HBGA，和唾液酸作为控制对ReCV感染的敏感性的关键细胞表面分子。所研究的所有ReCV分离株都需要CAR。然而,对不同碳水化合物分子的需求在不同的ReCV菌株之间变化。我们的发现对HuNoVs有直接意义。
