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Transfusion-related immunomodulation influences infectious disease outcomes

输血相关的免疫调节影响传染病的结果

基本信息

批准号：
10634538
负责人：
GRAHAM SIMMONS
金额：
$ 62.31万
依托单位：
VITALANT
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10634538
关键词：
Acute Adverse effects Alphavirus Animal Model Arboviruses Attenuated Back Blood Blood Donations Blood Transfusion Characteristics Chikungunya virus Collection Communicable Diseases Data Decision Making Disease Disease Outcome Dose Epidemic Equilibrium Event FDA approved Goals Hand Human Immune Immune response Immune system Immunocompetent Immunologic Factors Infection Intervention Intravenous Knockout Mice Knowledge Lymphoid Cell Mediating Modeling Molecular Mus Outcome Packed Red Blood Cell Transfusion Pathogenesis Pathogenicity Pathway interactions Plasma Platelet Transfusion Public Health Puerto Rico RNA Regulatory T-Lymphocyte Reporting Ross river virus Safety Symptoms Testing Therapeutic Transfusion Transfusion-Transmitted Virus Vascular blood supply Viral Viral Load result Viral Pathogenesis Viremia Virus Virus Diseases Virus Replication Zika Virus acute infection acute symptom adverse outcome arthropod-borne attenuation cell type chikungunya chikungunya infection cost effectiveness cytokine epidemic virus human model immunoregulation improved in vitro Assay infection rate mosquito-borne mouse model new epidemic reduce symptoms response screening tool transmission process viral RNA

项目摘要

Project Summary/Abstract Transmission of acute viral infections through blood transfusion during large epidemics is a serious public health issue, particularly for newly emerging infections for which no sensitive FDA-approved tests are available. Arboviruses can be serious acute infections leading to serious long-term complications, and are noted for their massive epidemic, as recently demonstrated with first chikungunya virus (CHIKV) and then Zika virus. Despite possessing many of the characteristics required for blood transfusion transmission (TT), such as high loads of infectious virus in blood and the ability to infect via intravenous inoculation, there have never been any CHIKV TT events reported. This is despite large-scale epidemics where up to 2% of blood donations have been found to be RNA reactive. We have preliminary data supporting the fact that CHIKV can be transfusion-transmitted in mice, and that transfusion of RBC attenuated CHIKV pathogenesis. The central hypothesis behind this study is that TT does occur, however a number of factors drive infection towards being asymptomatic or mild. Further, immune modulation during transmission, in this case via the blood transfusion itself, leads to an attenuation of disease. Specifically, we and others have demonstrated a number of innate immune factors are both modulated by transfusion and able to alter CHIKV outcomes. These include innate lymphoid cells and regulatory T cells and the cytokines both upstream and downstream of their stimulation. This study will use a murine model of CHIKV pathogenesis to investigate these findings further. Additionally, it will mimic blood transfusions, TT of CHIKV, and study immune parameters and disease outcomes. Beyond understanding the interplay between pathogenesis and blood transfusion, these studies will have a wider impact on acute viral infections in general. It is likely that similar immune factors can have dramatic effects on viral replication and/or pathogenesis, and thus a deeper understanding of how these mechanisms are mediated will allow better planning for screening efforts and potentially even interventions during serious epidemics. This will allow improved capabilities and decision making in responding rapidly to a new viral threat to blood safety and availability.

项目总结/文摘