GENETIC DIVERSITY AMONG RHESUS ENTERIC CALICIVIRUSES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 诺如病毒（Noroviruses，NV）是重要的人类病原体，但由于缺乏有效的组织培养或动物模型，NV的研究长期受到阻碍。最近我们报道了一种可培养杯状病毒（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，电视和NV之间的密切相似性，就其生殖，流行病学和组织血型抗原（HBGA）的结合，使电视系统的一个有前途的模型，为人类NV胃肠炎。在这项研究中，325个随机选择的粪便样本收集的TNPRC恒河猴的杯状病毒的存在下，通过使用一个修改的简并引物组（P289/P290）靶向杯状病毒RNA依赖的RNA聚合酶（RdRp）的保守氨基酸基序进行测试。三十六（11%）的325个粪便样本测试产生了电视的特定序列，表明电视是地方性的TNPRC殖民地。系统发育分析表明，36个TV分离物可分为两个基因组和至少4个基因型。有趣的是，没有一个菌株与2004年从同一个菌落中分离出的原型TV相同。 恒河猴肠杯状病毒之间的这种广泛的遗传多样性表明，在TNPRC殖民地的TV的流行病学和演变是类似的人类NV，可能与广泛的宿主和免疫压力（群体免疫）的HBGA库。因此，恒河猴肠道杯状病毒可以作为一个模型的进化和流行病学的人类NV。TV遗传多样性与这些病毒的组织培养适应性的发现是重要的，因为它打开了研究遗传变异和血清型（抗原型）之间的关系与NV疫苗和诊断检测开发的应用程序的途径。

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.