Enhancing Innate Anti-Viral Resistance Through A Community-Based Intervention

通过基于社区的干预措施增强先天抗病毒抵抗力

基本信息

批准号：
10360827
负责人：
STEVE W COLE
金额：
$ 63.9万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-15 至 2027-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10360827
关键词：
2019-nCoV Address African American African American population Age Antibodies Antiviral Response Antiviral resistance Basic Science Biochemical Biological Biological Factors Biological Process Biology COVID-19 COVID-19 pandemic Cells Chronic Disease Clinical Communities Coronavirus Cytotoxic T-Lymphocytes Dendritic Cells Disease Educational Background Gene Expression Gene Expression Regulation Gene Family Generations Genetic Transcription Genomics Goals HIV-1 Health Host resistance Human IL6 gene Immune In Vitro Individual Inflammation Inflammatory Inflammatory Response Influenza Interferon Type I Interferons Intervention Intervention Studies Intervention Trial Life Link Loneliness Maps Measures Mediator of activation protein Mentors Obesity Older Population Overweight Pathology Pathway interactions Personal Satisfaction Persons Physical activity Pilot Projects Population Process Public Health Randomized Randomized Controlled Trials Regulator Genes Research Resistance Resistance to infection Risk Factors Signal Transduction Sleep Social isolation Social support Stress Sympathetic Nervous System T cell response TNF gene Testing Urban Community Virus Diseases Vulnerable Populations Woman active control age effect arm base biobehavior biological adaptation to stress cell type coronavirus disease disadvantaged population falls fighting infection rate intergenerational intervention program low socioeconomic status men monocyte poor sleep primary endpoint primary outcome programs psychosocial racial disparity resilience respiratory infection virus respiratory virus response secondary endpoint secondary outcome sex social social disadvantage social engagement social interventions sociodemographic group sociodemographics socioeconomic disadvantage transcription factor vaccine response

项目摘要

Project Summary The SARS-CoV-2/COVID-19 pandemic has disproportionately impacted older socioeconomically disadvantaged African-Americans. This research will test whether a recently developed community-based intervention program known as Generation Exchange (GenX) can enhance a key biological mediator of antiviral resistance (Type I interferon response) in this disadvantaged population. Our previous research has identified a stress-triggered genomic program known as the “Conserved Transcriptional Response to Adversity” (CTRA). The CTRA is activated by fight-or-flight stress responses and causes immune cells to reduce antiviral activity and stimulate inflammation, both of which are detrimental in the context of COVID- 19. Our previous research on biological resilience in the face of adversity has also found that the CTRA is reduced in people with high levels of eudaimonic well-being, which includes purpose in life, generativity, and pro-social engagement. In the present study, we will conduct a randomized controlled intervention trial (n=160) to test whether a eudaimonia-promoting intergenerational mentoring program known as Generation Xchange (GenX) can enhance Type I interferon responses and reduce hyper-inflammatory responses in older African-American women and men living in a socioeconomically disadvantaged urban community. Our hypotheses are that GenX will, 1) increase Type I interferon antiviral responses, 2) reduce hyper-inflammatory bias, and 3) reduce rates of clinical respiratory virus infection and symptomatic disease (COVID, influenzas, and colds). To identify the biological mechanisms of antiviral resistance in this specific population, we will also analyze specific antiviral cell types (e.g., plasmacytoid dendritic cells, monocytes) and gene regulatory processes (e.g., transcription factor activity and single-cell gene expression). These measures will be used to determine 4) which biological factors are most important in protecting older African-Americans from respiratory virus infection, 5) how those biological risk factors are linked to other established respiratory virus risk factors (e.g., overweight/obesity, pre-existing chronic disease, low physical activity, poor sleep, social isolation/loneliness), and 6) which biological factors are impacted by GenX. Finally, we test the hypothesis that 7) GenX will show positive effects for both women and men, for those with low or high education level, and for those with low or high levels of background risk factors (e.g., overweight/obesity, chronic disease, low physical activity, social isolation/loneliness). Our overarching goal is to establish a community-based biobehavioral intervention program that is broadly scalable, involves defined biological mechanisms of antiviral resistance, and leverages social support and eudaimonic well-being to mitigate the detrimental effects of age and social disadvantage on host resistance to respiratory virus infection among COVID-vulnerable older African-Americans.

项目摘要 SARS-COV-2/COVID-19大流行对较老的社会经济影响不成比例不利的非裔美国人。这项研究将测试最近开发的基于社区的干预计划已知为生成交换（GENX）可以增强关键的生物介体在此灾难人群中，抗病毒药抗性（I型干扰素反应）。我们以前的研究已经确定了一个被压力触发的基因组程序，称为“对逆境”。降低抗病毒活性并刺激感染，这两者在共同的背景下都是有害的 19。我们先前关于面对广告的生物弹性的研究还发现，CTRA是较高的Eudaimonic幸福感的人减少了，其中包括生命的目的，发电性，和亲社会参与。在本研究中，我们将进行随机控制的干预措施试验（n = 160）测试是否促进Eudaimonia促进的代际心理计划 Xchange（GenX）一代可以增强I型干扰素反应并减少过度炎症居住在社会经济处境不利的城市中的非洲裔美国妇女和男性的回应社区。我们的假设是Genx将是1）增加I型干扰素抗病毒反应，2）减少过度炎性偏见，3）降低临床呼吸道病毒感染和症状的率疾病（COVID，影响力和感冒）。确定抗病毒抗性的生物学机制该特定种群，我们还将分析特定的抗病毒细胞类型（例如，静脉细胞树突状细胞，单核细胞）和基因调节过程（例如，转录因子活性和单细胞基因表达）。这些措施将用于确定4）哪些生物学因素在保护年长的非裔美国人免受呼吸道病毒感染，5）这些生物危险因素如何与其他已建立的呼吸道病毒危险因素有关（例如，超重/肥胖症，预先存在的慢性疾病，体育锻炼低，睡眠不良，社会隔离/孤独感）和6）哪些生物因素是受Genx的影响。最后，我们检验了以下假设：7）Genx对两名女性都会表现出积极影响对于那些低或高等教育水平的人，对于那些背景低或高水平的人危险因素（例如，超重/肥胖，慢性病，身体活动低，社会隔离/孤独感）。我们的总体目标是建立一个基于社区的生物行为干预计划可扩展，涉及抗病毒抗性的定义生物学机制，并利用社会支持和 Eudaimonic幸福感减轻了对主机的年龄和社会灾难的有害影响可抗性的老年非裔美国人对呼吸道病毒感染的抗性。