GENETIC DIVERSITY AMONG RHESUS ENTERIC CALICIVIRUSES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 诺如病毒(NoroVirus，NV)是重要的人类病原体，但长期以来，由于缺乏有效的组织培养或动物模型，NV的研究一直受到阻碍。最近我们报道了一种可培养的杯状病毒(杜兰病毒；TV)的发现。通过我们正在进行的研究获得的初步结果显示，TVS和NVS在系统发育、流行病学和组织血型抗原(HBGA)结合方面非常相似，这使得TV系统成为人类NV胃肠炎的一个有前途的模型。本研究从TNPRC恒河猴粪便标本中随机选取325份样本，使用针对杯状病毒RNA依赖RNA聚合酶(RdRp)中保守氨基酸基序的改良简并引物(P289/P290)检测杯状病毒的存在。在测试的325份粪便样本中，36份(11%)产生了TV特异性序列，表明TVS在TNPRC群体中是地方性的。根据系统发育分析，36株TV毒株可分为两个基因群和至少四个遗传类型。有趣的是，这些菌株都不与2004年从同一菌落分离的原型电视完全相同。恒河猴肠道杯状病毒的如此广泛的遗传多样性表明，TNPRC群体中TVS的流行病学和进化与人类NV相似，可能与宿主的广泛HBGA谱系和免疫压力(群体免疫)有关。因此，恒河猴肠道杯状病毒可以作为研究人类新城疫病毒进化和流行病学的模型。这些病毒具有组织培养适应性的TV基因多样性的发现具有重要意义，因为它为研究基因变异与血清型(抗原型)之间的关系以及在NV疫苗和诊断方法开发中的应用开辟了道路。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Noroviruses (NV) are important human pathogens, however NV research has been long time hampered by the lack of an efficient tissue culture or animal model. Recently we reported the discovery of a cultivable calicivirus (Tulane virus; TV). Preliminary results obtained through our ongoing studies show close similarities between TVs and NVs in respect to their phylogeny, epidemiology and histo-blood group antigen (HBGA) binding that make the TV system a promising model for human NV gastroenteritis. In this study 325 randomly selected stool samples collected from TNPRC rhesus macaques were tested for the presence of caliciviruses by using a modified degenerated primer set (P289/P290) targeting conserved amino acid motifs in the calicivirus RNA dependent RNA polymerases (RdRp). Thirty six (11%) of the 325 stools samples tested yielded TV specific sequences, indicating that TVs are endemic in the TNPRC colony. According to phylogenetic analysis, the 36 TV isolates can be classified into two genogroups and at least four genetic types. Interestingly, none of the strains were identical to the prototype TV that was isolated from the same colony in 2004. Such wide genetic diversity among rhesus enteric caliciviruses indicates that the epidemiology and evolution of TVs in the TNPRC colony are similar to those of human NVs, possibly associated with wide HBGA repertoire of the host and immune pressure (herd immunity). Thus, rhesus enteric caliciviruses could be used as a model for the evolution and epidemiology of human NVs. The discovery of TV genetic diversity with the tissue culture adaptability of these viruses is important because it opens the avenue for studying the relationship between genetic variation and serotypes (antigenic types) with applications to NV vaccine and diagnostic assay development.