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Placental Immunity to LCMV

胎盘对 LCMV 的免疫

基本信息

批准号：
7776884
负责人：
ELIZABETH A. BONNEY
金额：
$ 27.56万
依托单位：
UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-05-01 至 2011-06-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7776884
关键词：
Abortion Rates Activities of Daily Living Acute Affect Alphavirus Animals Antigens Antiviral Agents Area Biological Assay Birth Blood Circulation C57BL/6 Mouse CD8B1 gene Cells Cessation of life Chickenpox Cytomegalovirus Data Development Drug effect disorder Exhibits Experimental Models Face Failure Fetus Future Generations Growth Histocytochemistry Human Immune Immune response Immunity In Situ Individual Infection Kinetics Laboratories Lead Lymphoid Tissue MHC Class I Genes Maternal-Fetal Exchange Measures Mediating Memory Modeling Molecular Mothers Mus Natural Immunity Necrosis Outcome Parvovirus Peripheral Placenta Pregnancy Prevention Reagent Research Personnel Rubella Site System Systemic infection T cell response T memory cell T-Lymphocyte Technology Testing Thrombosis Time Tissues Tropism Tumor Necrosis Factor Ligand Superfamily Member 6 Uterus Vaccines Viral Viral Load result Viral Proteins Virus Virus Diseases West Nile virus adaptive immunity base cytokine experience fetal genetic selection genetic variant in vivo malformation novel peripheral blood placental transfer pregnant programs receptor response

项目摘要

We continue to be intrigued by several aspects of viral infection of the humanplacenta, including mechanism of infection, selectivity of infection, persistence or reemergence of infection, and outcome of infection. This last aspect is a particular challenge as infection with the same virus in different individuals, independent of viral load, can be associated with no effect, or fetal loss, malformation or growth abnormalities. Based on existing data about human infection with Cytomegalovirus, Rubella, and Parvovirus we assert that placental and viral factors, as well as maternal immunity affect the overall outcome of viral infection during pregnancy. Our experimental model uses Lymphocyticchoriomeningitis virus (LCMV) infection in C57BL/6 mice. Preliminary data in this model suggests that the systemic immuneresponse to LCMV, including generation of an antigen-specific memory T-cell pool during pregnancy is not different than in a non-pregnant state. However, pregnant animals, although able to clear the virus from the systemic circulation and several tissues, were not able to clear virus from the placenta before delivery and experienced a high rate of abortion. Some fetuses, completing gestation and isolated just before birth from mothers who were infected but cleared virus, also were negative for virus. This was true despite continued infection of their placentas. Infection of the placenta with LCMV is poorly understood mechanistically. Moreover, the immuneresponse to LCMV at the maternal-fetal interface has not been well characterized with the existing technology. However, both cellular infection and immune response have been extensively studied in lymphoid tissues and peripheral blood, and these studies will guide our experimental approach. Our hypothesis is that there is special tropism forLCMV in the placenta, and that this contributes significantly to the apparent difference in placental and systemic immune responses to LCMV. This application proposes development and use of new reagents and systems and immuno-histochemistry to i) delineate the local T cell response to LCMV infection of the placenta ii) determine the cellular and molecular consequences of LCMV infection at maternal-fetal interface and iii) investigate a novelplacenta!mechanism supporting high viral load after systemic infection The results will lead to a better understanding of antigen specific T cell immunityat this site and may guide development of future treatment and vaccines against agents causing persistent infectionof the placenta.

我们继续对病毒感染人类胎盘的几个方面感兴趣，包括机制