Study of Novel Influenza C Virus

描述(申请人提供)：正粘病毒有三种类型的流感病毒，被称为A，B和C，根据其核蛋白(NP)和基质1(M1)蛋白之间的抗原性差异进行分类，正如传统的血清学分析所证明的那样。我们从出现流感样疾病的猪身上鉴定出一种新的流感病毒。其氨基酸序列与ICV的同源性约为50%。系统发育分析进一步发现，该病毒与ICV关系最为密切，而与IAV和IBV关系不大。然而，新病毒与ICV之间的距离在大多数基因组片段上与IAV和IBV的差异相似。最近，我们也发现了C/OK类病毒在牛中的流行。C/OK和C/OK类病毒在牛和猪中的出现为跨物种传播提供了强有力的证据，突显了它们对人类健康的潜在威胁，因为人与这些农场动物之间有密切的身体接触。此外，这组病毒可能会与目前流行的人类ICV进行重新分类，以产生可能对人类和动物健康构成威胁的新的抗原变异体。对人类健康的潜在影响以及生物学和分子遗传学上的新特性值得对这组新病毒进行进一步研究，这构成了R21建议的基础。R21项目的主要目标是开发针对这些新病毒的反向遗传学系统(RGS)，鉴定它们的受体，阐明病毒HE蛋白在细胞嗜性和病毒复制温度限制中的功能作用，确定病毒突变率，并重要地确定人类ICV和这些新病毒是否可以进行重组以产生活病毒。该项目的成功完成将为这组对人类健康构成潜在威胁的新出现病毒的进化、生物学和遗传学提供新的见解。

DESCRIPTION (provided by applicant): The Orthomyxoviruses have three types of influenza viruses, termed as A, B, and C, that are classified according to the antigenic differences between their nucleoprotein (NP) and matrix 1 (M1) proteins as demonstrated in the traditional serological assays. We identified a novel influenza virus from swine exhibiting influenza-like illness. Its overall amino acid sequence shares approximately 50 % identity with that of ICV. Phylogenetic analysis further found that it is most closely related to ICV, rather than to IAV and IBV. However, the distance between the new virus and ICV was similar to the differences between IAV and IBV for the most of genomic segments. Recently, we also found the prevalence of C/OK-like virus in cattle. The incidences of C/OK and C/OK-like viruses in both cattle and swine provides strong evidence of cross-species transmission, highlighting their potential threat to human health because of closely physical contacts between humans and these farm animals. Additionally, this group of viruses may undergo reassortment with currently circulating human ICV to generate new antigenic variants that could pose a threat to human and animal health. The potential impact on human health and the novel properties in biology and molecular genetics warrant further investigation into this group of new viruses, which form the foundation of this R21 proposal. Major goals of this R21 project are to develop reverse genetics systems (RGS) for these novel viruses, identify their receptor, elucidate a functional role of vira HE protein in cell tropism and temperature restriction of virus replication, define viral mutation rates, and importantly determine whether human ICV and these new viruses can undergo reassortment to produce viable viruses. Successful completion of this project will provide novel insights to evolution, biology, and genetics of this new group of emerging viruses that have a potential threat to human health.