Study of a novel picornavirus genus associated with Acute Flaccid Paralysis

与急性弛缓性麻痹相关的新型小核糖核酸病毒属的研究

• 批准号: 8277184
• 负责人: Amit Kapoor
• 金额: $ 19.08万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-08 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8277184
• 关键词: Acute; Adult; Baculoviruses; Biological Assay; Capsid; Cell Culture Techniques; Cells; Child; Country; DNA; Data; Detection; Developing Countries; Development; Diagnostic Procedure; Disease; Enterovirus; Enzyme-Linked Immunosorbent Assay; Epidemiology; Etiology; Family Picornaviridae; Feces; Foundations; Frequencies; Future; General Population; Genetic; Genetic Drift; Genetic Variation; Genome; Genomics; Genotype; Goals; Health; High Prevalence; Human; Human Virus; Human poliovirus; Immunoglobulin G; Immunoglobulin M; Infection; Insecta; Intervention; Knowledge; Measures; Metagenomics; Molecular; Names; Paralysed; Pathogenesis; Pathogenicity; Phylogenetic Analysis; Polioviruses; Population; Prevalence; Production; Proteins; RNA; Reagent; Reporting; Role; Sampling; Sanitation; Satellite Viruses; Sequence Analysis; Serologic tests; Serological; Seroprevalences; Serum; Source; Surveillance Program; System; Testing; Time; Trauma; Vaccination; Variant; Viral; Viral Antigens; Viral Load result; Virion; Virus; Virus-like particle; cohort; design; disease transmission; expression vector; genetic analysis; genetic epidemiology; genome sequencing; infancy; member; novel; particle; pathogen; prevent; prototype; tissue culture; transmission process; virus genetics

DESCRIPTION (provided by applicant): In 2008 alone, 85,400 cases of acute flaccid paralysis (AFP) were reported from the countries with active poliovirus surveillance programs, of which less than 1,731 (2.03%) were found to be associated with poliovirus infection. Using a metagenomic approach we have discovered a group of highly divergent picornaviruses in children suffering from non-polio AFP. The complete genomes of six new viruses were sequenced and phylogenetic analysis indicated them to be sufficiently divergent from all currently known picornaviruses to form a new genus in the Picornaviridae family. In order to begin testing whether these new viruses, named Human Cosavirus (HCoSV), were a significant pathogen associated with non-polio AFP we tested stool samples from 160 non-polio AFP cases using specific PCR primers. HCoSV RNA was detected in stool samples of 107 AFP cases. High prevalence and high viral load of HCoSV variants in stool samples of multiple AFP children leads us to hypothesize that HCoSV is a human pathogen associated with AFP in children. Initial phylogenetic analysis of HCoSV variants showed the existence of four different viral species within this new Picornaviridae genus. The level of genetic divergence between species of genus Cosavirus was similar to that between species of genus Enterovirus. Further information regarding HCoSV genetic diversity and epidemiology is now required to clarify its pathogenic role in AFP and, if confirmed, for developing strategies to prevent its transmission and disease. AIM 1 will determine the prevalence of different HCoSV genotypes in samples from a larger number of AFP cases plus demographically matched healthy controls to test whether there is a significant association with AFP, followed by full genome genetic characterization of the most divergent HCoSV variants. AIM 2 will be the development of a serological assay for HCoSV using virions produced by cell culture or viral capsids derived from baculovirus/insect cell expression. AIM 3 will determine the prevalence of seroreactivity to HCoSV in AFP cases, in healthy controls and in the general population. This exploratory study of a new human picornavirus genus that we have recently characterized and detected at high frequency in developing countries will therefore provide the foundation for possible steps to relieve the still high health burden imposed by infantile paralytic diseases. Our long-term goal is to define the pathogenic potential of HCoSV and to prevent new infections.

描述（由申请人提供）：仅在2008年，有85,400例急性松弛瘫痪（AFP）的据报道，有活跃的脊髓灰质炎病毒监测计划的国家，其中少于1,731（2.03％）与肺炎病毒感染有关。使用宏基因组方法，我们发现了患有非Polio AFP的儿童中的一组高度分歧的Picornavirus。对六种新病毒的完整基因组进行了测序，系统发育分析表明它们与当前所有已知的Picornavires的分歧足够分歧，可以在Picornaviridae家族中形成新属。为了开始测试这些新病毒（HCOSV）是否是与非Polio AFP相关的重要病原体，我们使用特定的PCR引物测试了来自160个非Polio AFP病例的粪便样品。在107例AFP病例的粪便样品中检测到HCOSV RNA。多个AFP儿童的粪便样品中HCOSV变体的高流行率和高病毒载量导致我们假设HCOSV是与儿童AFP相关的人类病原体。 HCOSV变体的最初系统发育分析表明，在这种新的Picornaviridae属中存在四种不同的病毒物种。果酱属种类之间的遗传差异水平与肠道病毒属之间的遗传差异相似。现在需要有关HCOSV遗传多样性和流行病学的更多信息，以阐明其在AFP中的致病作用，并确认，以制定防止其传播和疾病的策略。 AIM 1将确定来自大量AFP病例加上人口统计学匹配的健康对照的样品中不同HCOSV基因型的患病率，以测试是否与AFP存在显着关联，然后是最不同的HCOSV变体的完全基因组遗传表征。 AIM 2将使用由细胞培养物或源自杆状病毒/昆虫细胞表达的病毒式衣壳产生的病毒体开发用于HCOSV的血清学分析。 AIM 3将确定在AFP病例，健康对照和普通人群中对HCOSV的静脉反应率的普遍性。因此，这项对我们最近在发展中国家在高频中表征和检测到的新的人类Picornavirus属的探索性研究将为减轻婴儿麻痹性疾病施加的仍然很高的健康负担提供基础。我们的长期目标是定义HCOSV的致病潜力并防止新的感染。

项目成果

The serological evidence in humans supports a negligible risk of zoonotic infection from porcine circovirus type 2.

• DOI: 10.1016/j.biologicals.2013.09.005
• 发表时间: 2013-11
• 期刊: BIOLOGICALS
• 影响因子: 1.7
• 作者: Burbelo, Peter D.;Ragheb, Jack A.;Kapoor, Amit;Zhang, Yanjin
• 通讯作者: Zhang, Yanjin

Altered antibody profiles against common infectious agents in chronic disease.

• DOI: 10.1371/journal.pone.0081635
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Burbelo PD;Ching KH;Morse CG;Alevizos I;Bayat A;Cohen JI;Ali MA;Kapoor A;Browne SK;Holland SM;Kovacs JA;Iadarola MJ
• 通讯作者: Iadarola MJ