A Guinea Pig Model of Adenovirus Pneumonia

腺病毒肺炎豚鼠模型

• 批准号: 7781376
• 负责人: Adriana Elisa Kajon
• 金额: $ 32.08万
• 依托单位: LOVELACE BIOMEDICAL & ENVIRONMENTAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-15 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7781376
• 关键词: Acute; Acute respiratory infection; Address; Adenovirus Infections; Adenoviruses; Adult; Animal Model; Antiviral Agents; Applications Grants; Biological; Biological Assay; Biology; Biomedical Research; Cavia; Cavia porcellus; Characteristics; Child; Child Mortality; Clinical; Detection; Development; Diagnosis; Diagnostic; Disease; Disease Outbreaks; Etiology; Exhibits; Genome; Goals; Hospitalization; Human; Immunocompromised Host; In Vitro; Infection; Infectious Agent; Intervention; Laboratory Animals; Lung; Lung diseases; Modeling; Molecular; Pathogenesis; Pneumonia; Publications; Publishing; Qualifying; Quality Control; Reporting; Research; Research Personnel; Resources; Respiratory Tract Infections; Rodent; Role; Sampling; Serotyping; Study models; System; Testing; Therapeutic Agents; Therapeutic Intervention; Time; Titrations; United States; Viral; Viral load measurement; Virulence; Virus; animal colony; base; design; fitness; in vivo; innovation; killings; mortality; novel; pathogen; programs; public health relevance; research study; respiratory; tool; virus host interaction

DESCRIPTION (provided by applicant): General Summary Adenoviruses (Ads) are among the most prevalent causative agents of respiratory disease requiring hospitalization in both children and adults, and have been widely recognized as important opportunistic pathogens for immunocompromised patients. Despite the important role of Ads in the etiology of human respiratory disease, relatively little is known about the molecular bases of their unique pathobiology. The lack of a permissive animal model of Ad respiratory infection has hampered the understanding of the molecular mechanisms underlying the frequently observed complications of Ad-associated severe respiratory illness such as disseminated infection with extrapulmonary clinical manifestations, and long-term pulmonary sequelae, and has precluded the testing of systemic antivirals and other therapeutic agents in vivo. This developmental grant application will address the characterization of guinea pig adenovirus (GPAdV) infection of its natural host, Cavia porcellus, as a novel surrogate model of mammalian adenovirus respiratory infection. GPAdV is a natural respiratory pathogen of guinea pigs but remains a virtually uncharacterized virus due to the lack of suitable in vitro systems for viral isolation. Three specific aims will be pursued: 1: To sequence and annotate the genome of GPAdV, 2: To develop assays for the detection of GPAdV and titration of infectious virus load in experimental samples, and 3: To delineate the basic characteristics of GPAdV respiratory infection in its natural host, Cavia porcellus. The proposed research is innovative because it examines for the first time a new mammalian adenovirus that causes acute respiratory disease in its natural host as a model of adenovirus pathogenesis. These studies will break new ground toward the understanding of the pathobiology of mammalian adenovirus respiratory infections, and provide resources for the diagnosis and management of an important infectious agent of laboratory animals. PUBLIC HEALTH RELEVANCE: The lack of a permissive animal model of adenovirus respiratory infection has hampered the understanding of the mechanisms and virus-host interactions underlying the frequently observed complications of adenovirus- associated severe respiratory illness, and has precluded the testing of antivirals and other therapeutic agents in vivo. The proposed study will develop a permissive mammalian model of adenovirus pneumonia using guinea pig adenovirus (GPAdV) and its natural host, Cavia porcellus, and will thus provide a new resource for design and testing of intervention strategies. In addition, these studies will break new ground toward the understanding of the pathobiology of mammalian adenovirus respiratory infections, and generate resources for the diagnosis and management of a prevalent infectious agent of laboratory animals used in biomedical research.

描述（由申请方提供）：一般概述腺病毒（Ad）是儿童和成人中需要住院治疗的呼吸系统疾病的最常见病原体之一，并且已被广泛认为是免疫功能低下患者的重要机会致病菌。尽管广告在人类呼吸道疾病的病因学中发挥着重要作用，但对其独特的病理生物学的分子基础知之甚少。缺乏一个许可的动物模型的Ad呼吸道感染，阻碍了了解的分子机制的基础上经常观察到的并发症的Ad相关的严重呼吸道疾病，如播散性感染与肺外的临床表现，和长期的肺部后遗症，并排除了测试全身抗病毒药物和其他治疗药物在体内。该开发资助申请将解决豚鼠腺病毒（GPAdV）感染其天然宿主豚鼠（Cavia porcellus）的特性，作为哺乳动物腺病毒呼吸道感染的新型替代模型。GPAdV是豚鼠的天然呼吸道病原体，但由于缺乏用于病毒分离的合适的体外系统，其仍然是实际上未表征的病毒。将追求三个具体的目标：1：测序和注释的基因组的GPAdV，2：开发用于检测GPAdV和滴定的实验样品中的感染性病毒载量的测定法，和3：描绘GPAdV呼吸道感染的基本特征，在其天然宿主，豚鼠。这项研究具有创新性，因为它首次研究了一种新的哺乳动物腺病毒，这种腺病毒在其自然宿主中引起急性呼吸道疾病，作为腺病毒发病机制的模型。这些研究将为了解哺乳动物腺病毒呼吸道感染的病理生物学开辟新天地，并为诊断和管理实验动物的重要传染病提供资源。公共卫生关系：缺乏腺病毒呼吸道感染的容许动物模型阻碍了对腺病毒相关的严重呼吸道疾病的常见并发症的机制和病毒-宿主相互作用的理解，并且阻碍了体内抗病毒药物和其他治疗剂的测试。拟议的研究将开发一个允许的哺乳动物模型的腺病毒肺炎使用豚鼠腺病毒（GPAdV）和它的天然宿主，豚鼠，因此将提供一个新的资源设计和测试的干预策略。此外，这些研究将为理解哺乳动物腺病毒呼吸道感染的病理生物学开辟新的天地，并为生物医学研究中使用的实验室动物的流行感染因子的诊断和管理提供资源。

项目成果

Genomic and phylogenetic analysis of two guinea pig adenovirus strains recovered from archival lung tissue.

从档案肺组织中回收的两种豚鼠腺病毒株的基因组和系统发育分析。

• DOI: 10.1016/j.virusres.2020.197965
• 发表时间: 2020
• 期刊: Virus research
• 影响因子: 5
• 作者: Hofmann-Sieber,Helga;Gonzalez,Gabriel;Spohn,Michael;Dobner,Thomas;Kajon,AdrianaE
• 通讯作者: Kajon,AdrianaE

Isolation and initial propagation of guinea pig adenovirus (GPAdV) in Cavia porcellus cell lines.

豚鼠腺病毒 (GPAdV) 在​​豚鼠细胞系中的分离和初始繁殖。

• DOI: 10.12688/f1000research.20135.2
• 发表时间: 2019
• 期刊: F1000Research
• 作者: Kajon,AdrianaE;Li,Xiaoxin;Gonzalez,Gabriel;Core,Susan;Hofmann-Sieber,Helga;Leng,Shuguang
• 通讯作者: Leng,Shuguang