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

基本信息

批准号：
8486391
负责人：
JORGE C BLANCO
金额：
$ 23.83万
依托单位：
SIGMOVIR BIOSYSTEMS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-06-11 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8486391
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

项目摘要

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".

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 感染与相当严重的疾病相关，例如哮喘恶化、儿童喘息疾病和慢性阻塞性肺病 (COPD)。鼻病毒感染引起的发病率和死亡率相当高，每年造成数十亿美元的医疗费用。尽管这个问题很严重，但目前尚无有效预防 HRV 感染或治疗 HRV 相关疾病的方法。在许多物种（从小鼠到猴子）中开发 HRV 感染的小动物模型的尝试都失败了，从而严重阻碍了机制研究以及针对 HRV 感染的疫苗和治疗方法的开发。与实验室小鼠和大鼠不同，棉鼠（Sigmodon hispidus）对人类病毒感染表现出独特的易感性，已成为许多人类呼吸道病原体的首选模型，包括呼吸道合胞病毒（RSV）、流感（甲型和乙型）、腺病毒（几种血清型）、副流感病毒（3 型）和麻疹。该项目的长期目标是利用棉鼠建立可靠的HRV感染模型。基于有据可查的棉鼠对多种人类病毒的易感性以及我们自己的初步研究表明，HRV16 鼻内感染会导致棉鼠呼吸道病变，我们建议首先，描述棉鼠急性 HRV16 感染的特征棉鼠通过 (a) 定义 HRV16 感染的动力学； (b) 选择可用于追踪急性疾病的临床参数； (c) 描述 HRV16 诱导的上呼吸道和下呼吸道病理学； (d) 定义 HRV-16 感染引起的细胞因子和趋化因子的表达。其次，我们将重点研究棉鼠 HRV16 感染产生的保护性免疫反应的特征。我们已经组建了一支强大的研究团队，结合了棉鼠使用方面的丰富专业知识和强大的病毒学能力。如果成功，拟议的研究将产生测试针对“普通感冒”的疫苗和疗法的宝贵实验资源。