PATHOGENESIS OF MURINE PARVOVIRUS FIELD STRAINS

鼠细小病毒田毒株的发病机制

• 批准号: 7239644
• 负责人: DAVID G BESSELSEN
• 金额: $ 21.48万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-08 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7239644
• 关键词: Affect; Age; Animal Experimentation; Biocompatible Materials; Biology; Cells; Cessation of life; Clinical; Communicable Diseases; Congenital cerebellar hypoplasia; Diagnosis; Disease; Disruption; Ensure; Epidemiology; Explosion; Fertility; Gene Expression; Gene Transduction Agent; Generations; Hamsters; Hematopoiesis; Hematopoietic; Histologic; Immune; Immune response; Immune system; Immunosuppressive Agents; In Vitro; Inbred BALB C Mice; Infection; Infectious Agent; Institution; Intestines; Investigation; Kidney; Knockout Mice; Laboratories; Laboratory mice; Lesion; Literature; Mice Minute Virus; Molecular; Molecular Epidemiology; Molecular and Cellular Biology; Mouse Cell Line; Mouse Strains; Mus; Neonatal; Parvovirus; Pathogenesis; Pathology; Phenotype; Physiology; Prevalence; Prevention; Production; Range; Relative (related person); Reporting; Research; Research Personnel; Rodent; Role; Time; Vertical Disease Transmission; Viral; Viral Pathogenesis; Virus; Virus Diseases; base; epidemiology study; immunoregulation; in vivo; novel; programs; prototype; research facility; stressor; tissue tropism; tissue/cell culture; transmission process; virus host interaction; virus virus interaction

DESCRIPTION (provided by applicant): Minute virus of mice (MVM) and MPV are among the most prevalent infectious agents found in contemporary laboratory mouse colonies, and can potentially induce pathology, immunomodulation, or biomaterial contamination on the basis of experimentation with routine parvovirus laboratory strains. However, little is known about the strains of these viruses that are actually circulating in laboratory mouse colonies or the phenotypic effects associated with infection by these viral strains. Given the difficulties associated with murine parvovirus eradication, the high potential for their transmission among research facilities, and the rapidly expanding use of genetically altered mice, murine parvoviruses pose one of the most significant infectious disease problems in contemporary laboratory animal research. Several recently isolated or previously unrecognized strains of MVM and MPV have been obtained by our laboratory and shown to differ significantly from well characterized laboratory strains genetically, suggesting that in vivo infection by circulating field strains of MVM and MPV significantly differ from well characterized prototypic strains. The objectives of this proposal are to characterize the biology, epidemiology, pathogenesis, and host response to isolates of MVM and MPV that represent those circulating among contemporary laboratory mouse colonies. Three Specific Aims will be pursued: (1) Examine the prevalence of viral strains circulating within laboratory mouse colonies, isolate, and molecularly characterize strains that differ significantly from known strains, and characterize the in vitro host cell range for novel isolates and isolates already obtained; (2) Characterize the pathogenesis and transmission of murine parvovirus field strains to investigate the cellular and tissue tropism of viruses in various strains and ages of mice, the potential for persistent infection and reactivation of infectious virus production in persistently infected mice, and the potential for horizontal and vertical transmission; and (3) Characterize the host response to murine parvovirus field strains to investigate the humoral and cellular immune response, perturbations in hematopoiesis and host cell gene expression, the specific subpopulations of immune and hematopoietic cells infected by murine parvoviruses, and the roles of various immune system components on viral pathogenesis. These studies will provide critical information that can be applied to ensure accurate diagnosis, prevention of transmission, and eradication of these viruses from contemporary laboratory mouse colonies. In addition, these studies will provide information about perturbations in host physiology and gene expression induced by murine parvoviruses, and basic scientific information about parvovirus host interaction.

描述（由申请人提供）： 小鼠微小病毒 (MVM) 和 MPV 是当代实验室小鼠群体中发现的最流行的传染原，根据常规细小病毒实验室毒株的实验，可能会诱发病理、免疫调节或生物材料污染。 然而，人们对实验室小鼠群体中实际传播的这些病毒株或与这些病毒株感染相关的表型效应知之甚少。 鉴于根除鼠细小病毒的困难、其在研究机构之间传播的高潜力以及基因改造小鼠的迅速扩大使用，鼠细小病毒构成了当代实验动物研究中最重要的传染病问题之一。 我们的实验室已经获得了几种最近分离的或以前未被识别的 MVM 和 MPV 毒株，这些毒株与已充分表征的实验室毒株在遗传上存在显着差异，这表明 MVM 和 MPV 现场循环毒株的体内感染与已充分表征的原型毒株显着不同。 本提案的目的是描述当代实验室小鼠群体中流行的 MVM 和 MPV 分离株的生物学、流行病学、发病机制和宿主反应。 将追求三个具体目标：（1）检查实验室小鼠群体内循环的病毒株的流行情况，分离并分子表征与已知毒株显着不同的病毒株，并表征新型分离株和已获得的分离株的体外宿主细胞范围; （2）表征鼠细小病毒野毒株的发病机制和传播，研究病毒在不同毒株和年龄的小鼠中的细胞和组织趋向性、持续感染小鼠中持续感染和重新激活感染性病毒产生的潜力，以及水平和垂直传输； (3) 表征宿主对鼠细小病毒野毒株的反应，以研究体液和细胞免疫反应、造血和宿主细胞基因表达的扰动、鼠细小病毒感染的免疫和造血细胞的特定亚群以及各种免疫的作用病毒发病机制的系统组成部分。这些研究将提供关键信息，可用于确保准确诊断、预防传播和根除当代实验室小鼠群体中的这些病毒。 此外，这些研究将提供有关鼠细小病毒引起的宿主生理学和基因表达扰动的信息，以及有关细小病毒宿主相互作用的基本科学信息。

项目成果

Identification of novel murine parvovirus strains by epidemiological analysis of naturally infected mice.

通过对自然感染小鼠的流行病学分析鉴定新型鼠细小病毒株。

• 发表时间: 2006-06
• 作者: Besselsen, David G;Romero, Melissa J;Wagner, April M;Henderson, Kenneth S;Livingston, Robert S
• 通讯作者: Livingston, Robert S

Transmission probabilities of mouse parvovirus 1 to sentinel mice chronically exposed to serial dilutions of contaminated bedding.

小鼠细小病毒 1 型向长期暴露于连续稀释的受污染垫料的哨兵小鼠的传播概率。

• 发表时间: 2008-04
• 影响因子: 0.8
• 作者: Besselsen, David G;Myers, Erin L;Franklin, Craig L;Korte, Scott W;Wagner, April M;Henderson, Kenneth S;Weigler, Benjamin J
• 通讯作者: Weigler, Benjamin J

Temporal transmission studies of mouse parvovirus 1 in BALB/c and C.B-17/Icr-Prkdc(scid) mice.

小鼠细小病毒 1 在 BALB/c 和 C.B-17/Icr-Prkdc(scid) 小鼠中的时间传播研究。

• 发表时间: 2007-02
• 影响因子: 0.8
• 作者: Besselsen, David G;Becker, Michael D;Henderson, Kenneth S;Wagner, April M;Banu, Laila A;Shek, William R
• 通讯作者: Shek, William R

Embryo transfer rederivation of C.B-17/Icr-Prkdc(scid) mice experimentally infected with mouse parvovirus 1.

实验性感染小鼠细小病毒 1 的 C.B-17/Icr-Prkdc(scid) 小鼠的胚胎移植再衍生。

• 发表时间: 2008-08
• 影响因子: 0.8
• 作者: Besselsen, David G;Romero;Munger, Stephanie J;Marcus, Emily C;Henderson, Kenneth S;Wagner, April M
• 通讯作者: Wagner, April M

Experimental infection of mice with hamster parvovirus: evidence for interspecies transmission of mouse parvovirus 3.

仓鼠细小病毒小鼠的实验感染：小鼠细小病毒 3 种间传播的证据。

• 发表时间: 2010-04
• 影响因子: 0.8
• 作者: Christie, Rachel D;Marcus, Emily C;Wagner, April M;Besselsen, David G
• 通讯作者: Besselsen, David G