Development of the Cotton Rat Model of Rhinovirus Infection and Disease

棉鼠鼻病毒感染和疾病模型的建立

• 批准号: 8360839
• 负责人: JORGE C BLANCO
• 金额: $ 27.48万
• 依托单位: SIGMOVIR BIOSYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-11 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360839
• 关键词: 18 year old; Acute; Acute Disease; Adenoviruses; Animal Model; Animals; Antibodies; Antibody Formation; Asthma; Characteristics; Child; Chronic Obstructive Airway Disease; Clinical; Common Cold; Cotton Rats; Development; Disease; Elderly; Enterovirus; Exhibits; Family Picornaviridae; Goals; Health Care Costs; Human; Human Virus; Human poliovirus; Immunoglobulin G; Inbreeding; Individual; Infection; Influenza; Kinetics; Laboratory Rat; Laboratory mice; Lower respiratory tract structure; Lung; Measles; Measures; Modeling; Molecular Profiling; Monkeys; Morbidity - disease rate; Mus; Nose; Para-Influenza Virus Type 3; Paralysed; Pathology; Phase; Polioviruses; Predisposition; Prevention; Research; Research Personnel; Resources; Respiratory System; Respiratory syncytial virus; Respiratory tract structure; Rhinovirus; Rodent; Secretory Immunoglobulin A; Serological; Serotyping; Serum; Severities; Sigmodon; Spinal Cord; Testing; Time; Trachea; Viral; Virus Diseases; Wheezing; animal model development; attributable mortality; base; chemokine; cytokine; flu; human subject; pathogen; respiratory; response; therapeutic vaccine; vaccine development; vaccine evaluation; virology

DESCRIPTION (provided by applicant): Human rhinoviruses (HRVs) are the most common cause of colds and flu-like illnesses. In addition, HRV infections are associated with disease of considerable severity, such as exacerbation of asthma, wheezing illness in children, and chronic obstructive pulmonary disease (COPD). The morbidity and mortality attributable to rhinovirus infection is considerable and results in billions of dollars of health care cost every year. Despit the significance of the problem, no effective prevention of HRV infection or treatment of HRV-associated disease is currently available. Attempts to develop a small animal model of HRV infection in many species, from mice to monkeys, have failed, thus severely hampering mechanistic studies and the development of vaccines and therapeutics against HRV infection. Unlike the laboratory mouse and rat, the cotton rat (Sigmodon hispidus) exhibits a unique susceptibility to infection by human viruses and has become a preferred model for a number of human respiratory pathogens including respiratory syncytial virus (RSV), influenza (A and B), adenoviruses (several serotypes), parainfluenza virus (type 3), and measles. The long term goal of this project is to use the cotton rat to establish a reliable model of HRV infection. Based on the well-documented susceptibility of the cotton rat to a diversity of human viruses and our own preliminary studies indicating that intranasal infection with HRV16 results in respiratory tract pathology in the cotton rat we proposed to First, Delineate the characteristics of acute HRV16 infection in cotton rats by (a) defining the kinetics of HRV16 infection; (b) selecting clinical parameters that can be use to follow acute disease; (c) describing the HRV16-induced pathology of the upper and lower respiratory tract; and (d) defining the expression of cytokines and chemokines resulting from HRV-16 infection. Secondly, we will focus in the characterization of the protective immunological response generated by HRV16 infection in the cotton rats. A strong team of investigators has been assembled combining extensive expertise in the use of cotton rats and strong virology capabilities. If successful, the proposed research will result in a valuable experimental resource to test vaccines and therapeutics against the "common cold". PUBLIC HEALTH RELEVANCE: Human rhinoviruses are the cause of most common colds and flu-like illnesses. In addition rhinovirus infections are associated with disease of considerable severity, such as exacerbation of asthma, wheezing illness in children, and chronic obstructive pulmonary disease. Attempts to develop a small animal model of rhinovirus infection in many animal species have failed, thus severely hampering mechanistic studies and the development of vaccines and therapeutics against HRV infection. The purpose of this project is to generate for the first time a model of rhinovirus infection using the cotton rat

描述（由申请人提供）：人类鼻病毒（HRV）是感冒和流感样疾病的最常见原因。此外，HRV感染与严重程度相当严重的疾病有关，例如哮喘的加剧，儿童喘息疾病和慢性阻塞性肺部疾病（COPD）。可归因于鼻病毒感染的发病率和死亡率相当大，每年导致数十亿美元的医疗保健费用。鄙视问题的重要性，目前没有有效预防HRV感染或HRV相关疾病的治疗。从小鼠到猴子的许多物种中开发小型HRV感染的小动物模型的尝试已经失败，因此严重阻碍了机理研究以及疫苗和治疗剂的开发，以防止HRV感染。与实验室小鼠和大鼠不同，棉花大鼠（Sigmodon hispidus）表现出对人类病毒感染的独特敏感性，并已成为许多人类呼吸道病原体（包括呼吸综合病毒（RSV），流感（a和b））的首选模型。 ，腺病毒（几种血清型），Parainfluenza病毒（3型）和麻疹。该项目的长期目标是使用棉花大鼠建立可靠的HRV感染模型。基于棉花大鼠对多样化的人类病毒多样性的易感性和我们自己的初步研究表明，HRV16的鼻内感染会导致棉花大鼠的呼吸道病理学，我们首先提出，我们提出的是急性HRV16感染的特征（a）定义HRV16感染的动力学； （b）选择可用于急性疾病的临床参数； （c）描述上和下呼吸道的HRV16诱导的病理； （d）定义由HRV-16感染引起的细胞因子和趋化因子的表达。其次，我们将集中于棉花大鼠HRV16感染产生的保护性免疫反应的表征。一支强大的调查人员团队已经组合了在使用棉花大鼠和强大的病毒学能力方面的广泛专业知识。如果成功，拟议的研究将导致 有价值的实验资源，用于测试“普通感冒”的疫苗和治疗剂。 公共卫生相关性：人类鼻病毒是最常见的感冒和类似流感疾病的原因。另外，鼻病毒感染与严重程度相当严重的疾病有关，例如哮喘的加剧，儿童喘息疾病和慢性阻塞性肺部疾病。在许多动物物种中开发鼻病毒感染的小动物模型的尝试失败了，因此严重阻碍了机械性研究以及疫苗和治疗剂的开发，以防止HRV感染。该项目的目的是首次使用棉大鼠产生鼻病毒感染的模型