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REGULATION OF VIRAL INFECTIVITY

病毒感染性的调节

基本信息

批准号：
2064221
负责人：
WILLIAM A CAFRUNY
金额：
$ 8.89万
依托单位：
UNIVERSITY OF SOUTH DAKOTA
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-05-01 至 1995-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2064221
关键词：
active immunization antiviral antibody disease /disorder model intestinal mucosa laboratory mouse macrophage monoclonal antibody surface antigens virus cytopathogenic effect virus infection mechanism

项目摘要

This project will study the mammalian mucosal barrier to transmission of viral infection, using an established mouse model. The lactate dehydrogenase-elevating virus (LDV) causes a persistent infection in mice, and may be transmitted to uninfected mice during exposure to either free or cell-associated virus at a variety of body sites. Normal mice have a relative mucosal barrier which governs the minimum infectious dose (MID) of LDV, which is lower for rectal inoculation than for oral, ocular, or vaginal inoculation. LDV is an ideal virus for the proposed work, since within four days of inoculation with the virus, infection is easily determined by a blood enzyme measurement. Mucosal barriers to LDV at gastrointestinal (GI) and genital sites will be investigated during exposure of mice to both free and macrophage-associated virus, in order to construct a model for contrasting free and cell-associated MID's. This model will be significant because there is currently a need to better understand mechanisms which can potentially regulate the MID with respect to both types of viral transmission. The proposed work will determine whether viral protection at mucosal sites can be established following passive immunization of uninfected animals with monocional anti-LDV antibodies, or active immunization with normal allogeneic cell-surface antigens. Uninfected mice will receive intravenous injections of anti-LDV antibodies, or will be immunized with allogeneic macrophages prior to live virus exposure in the form of free virus of LDV-infected macrophages, and effects on the rate of infection will be determined. Virus localization studies will be carried out on mice exposed to LDV at GI or genital sites. Using fluorescence antibody analysis, the cells at these sites in which LDV initiates a primary infection will be localized. These results will lead to a better understanding of how the mucosal barrier to infection is initially broken down. The long-term objective of this work is to gain a better understanding of mucosal mechanisms of viral defense, and to develop strategies to enhance these mechanisms. This work has important implications for certain medically important viruses, such as human immunodeficiency virus, which may be transmitted at mucosal sites, and for which better preventive strategies are currently needed.

这个项目将研究哺乳动物的粘膜屏障，以防止病毒的传播病毒感染，使用已建立的小鼠模型。乳酸盐脱氢酶提升病毒(LDV)在中国引起持续感染小鼠，并可能在接触病毒期间传播给未感染的小鼠在不同的身体部位有游离的或细胞相关的病毒。正常小鼠有一种相对的粘膜屏障，它控制着最小的 LDV感染剂量(MID)，直肠接种低于用于口服、眼部或阴道接种。LDV是一种理想的病毒拟议的工作，因为在接种病毒的四天内，感染很容易通过血酶测定来确定。胃肠道(GI)和生殖器部位对LDV的粘膜屏障在小鼠暴露于自由和巨噬细胞相关病毒，以构建一种对比自由MID和细胞关联MID。此模型将意义重大，因为目前需要更好地理解潜在地可以对MID进行调节的机制病毒传播的类型。拟议的工作将决定是否在被动感染后，可建立粘膜部位的病毒保护用抗LDV单抗免疫未感染的动物，或用正常的同种异体细胞表面抗原主动免疫。未感染的小鼠将接受静脉注射抗LDV 抗体，或将在免疫前用同种异体巨噬细胞免疫 LDV感染的活体病毒以游离病毒的形式暴露巨噬细胞，以及对感染率的影响将被确定。将在暴露于LDV的小鼠身上进行病毒定位研究 GI或生殖器站点。使用荧光抗体分析，细胞在这些LDV引发初级感染的地点将是本地化。这些结果将使我们更好地理解粘膜对感染的屏障最初被打破。这项工作的长期目标是更好地了解病毒防御的粘膜机制，并制定策略以强化这些机制。这项工作具有重要的意义某些医学上重要的病毒，如人类免疫缺陷病毒，它可能在粘膜部位传播，对哪一种更好目前需要预防性战略。