SENDAI VIRUS INFECTION--RESISTANCE AND SUSCEPTIBILITY

仙台病毒感染——耐药性和易感性

基本信息

批准号：
3450535
负责人：
DAVID G BROWNSTEIN
金额：
$ 13.75万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-09-15 至 1986-09-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3450535
关键词：
B lymphocyte T lymphocyte gene expression genetic strain genotype immunosuppression interferons linkage mapping parainfluenza virus type 1 respiratory disorder virus diseases

项目摘要

Sendai virus is the cause of a prevalent and disruptive indigenous respiratory infection of laboratory mice. Acute morbidity and mortality may accompany naturally-occurring Sendai virus infections depending on the genotype of the host. Chronic immunosuppression is a putative subclinical sequelae of infection but the influence of host genotype is not known. The proposed studies will seek to determine the short- and long-term immunological consequences of experimental subclinical Sendai virus infection in mice of resistant and susceptible genotypes and to determine how genetic resistance to this virus is expressed. Methods used will include measures of cellular B and T cell responses to antigenic stimulation in infected and uninfected mice, viral induction of natural killer cells, interferon and antigen-specific T and B cells in genetically resistant and susceptible mice, and virus replication in target tissues of resistant and susceptible mice. Preliminary genetics studies indicate that resistance to the lethal effects of Sendai virus infection is controlled by at least three autosomal dominant alleles whose effects are probably additive. Long-term objectives will include a more accurate determination of the number of genes involved using recombinant inbred strains of mice, their linkage to typed loci, how these individual genes are expressed, and how these genes modulate the clinical and subclinical consequences of Sendai virus infection.

仙台病毒是造成普遍和破坏性土著的原因实验室小鼠的呼吸道感染。急性发病率和死亡率可能伴随着天然发生的仙台病毒感染宿主的基因型。慢性免疫抑制是一种假定的亚临床感染的后遗症，但宿主基因型的影响尚不清楚。这拟议的研究将寻求确定短期和长期实验亚临床仙台病毒的免疫学后果抗性和易感基因型的小鼠感染，并确定如何表达对该病毒的遗传抗性。使用的方法将包括对抗原抗原的细胞B和T细胞反应的测量刺激感染和未感染的小鼠，自然诱导病毒诱导杀伤细胞，干扰素和抗原特异性T和B细胞在遗传上抗性和易感小鼠，以及在目标组织中复制病毒抗性和易感小鼠。初步遗传学研究表明仙台病毒感染的致命作用的抗性受到控制至少三个常染色体显性等位基因可能是添加剂。长期目标将包括更准确的决心使用小鼠重组近交菌株所涉及的基因数量，它们与键入基因座的联系，如何表达这些单个基因以及这些基因如何调节临床和亚临床后果的仙台病毒感染。