Study of Novel Influenza C Virus

新型丙型流感病毒的研究

• 批准号: 8702788
• 负责人: FENG LI
• 金额: $ 21.5万
• 依托单位: SOUTH DAKOTA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-15 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8702788
• 关键词: Amino Acid Sequence; Animals; Antibodies; Biological; Biological Assay; Biology; Cattle; Cell Culture Techniques; Cells; Classification; Code; Coupled; Development; Dideoxy Chain Termination DNA Sequencing; Evolution; Exhibits; Family suidae; Ferrets; Foundations; Genetic; Genomic Segment; Goals; Gold; Growth; Health; Human; Human Virus; In Vitro; Incidence; Infection; Influenza; Influenza A virus; Influenza C Virus; Investigation; Livestock; Lung diseases; Methods; Molecular; Molecular Genetics; Mutation; Nucleoproteins; Oklahoma; Orthomyxoviridae; Phylogenetic Analysis; Porcine Influenza A Virus; Prevalence; Property; Proteins; RNA Sequences; RNA Splicing; Respiratory Tract Diseases; Reverse Transcriptase Polymerase Chain Reaction; Role; Sequence Analysis; Serological; Serum; Surveys; System; Techniques; Temperature; Tropism; Variant; Viral; Virion; Virus; Virus Replication; Work; experience; genetic evolution; genome sequencing; hemagglutinin esterase; hemagglutinin esterase fusion protein; influenzavirus; insight; novel; novel virus; pathogen; positional cloning; public health relevance; receptor; receptor binding; respiratory; swine influenza; tool; transmission process

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.

描述（由申请人提供）：正瘤病毒具有三种类型的流感病毒，称为A，B和C，它们根据其核蛋白（NP）和基质1（M1）蛋白之间的抗原差进行分类，如传统血清学评估所示。我们从猪表现出类似流感的疾病的猪中发现了一种新型的流感病毒。它的总体氨基酸序列与ICV的身份约为50％。系统发育分析进一步发现，它与ICV最密切相关，而不是与IAV和IBV相关。但是，新病毒和ICV之间的距离与大多数基因组段的IAV和IBV之间的差异相似。最近，我们还发现牛中C/OK样病毒的流行率。牛和猪中C/OK和C/OK样病毒的发生率提供了跨物种传播的有力证据，突出了它们对人类健康的潜在威胁，因为人类与这些农场动物之间的身体接触紧密。此外，这组病毒可能会与目前循环的人类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抗原变异。对人类健康的潜在影响以及生物学和分子遗传学的新特性需要进一步研究这一新病毒，这是该R21提案的基础。该R21项目的主要目标是为这些新型病毒开发反向遗传学系统（RGS），识别其受体，阐明Vira He蛋白在细胞质量和病毒复制的温度限制中的功能作用，定义病毒突变率，并重要地确定人类ICV和这些新病毒是否可以使人重新生成可爱的病毒性。该项目的成功完成将为这种新的新兴病毒的进化，生物学和遗传学提供新的见解，这些病毒对人类健康有潜在的威胁。