Alcohol's impact on immunological and virological profiles in HIV patients

酒精对艾滋病毒患者免疫学和病毒学特征的影响

• 批准号: 10245323
• 负责人: Qigui Q Yu
• 金额: $ 30.18万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10245323
• 关键词: Adherence; Alcohol abuse; Alcoholic Hepatitis; Alcoholic Liver Diseases; Alcoholic beverage heavy drinker; Alcohols; Bacterial Translocation; Basic Science; Biological Specimen Banks; Blood; Blood specimen; Cell physiology; Cells; Characteristics; Chronic; Clinical; Clinical Research; Collection; Cross-Sectional Studies; DNA; DNA Integration; Data; Development; Disease Outcome; Disease Progression; Drug resistance; Enrollment; Gastrointestinal tract structure; General Population; HIV; HIV Infections; HIV Seronegativity; HIV therapy; Health; Immune; Immunologic Markers; Immunologics; Individual; Inflammation; Inflammatory; Infrastructure; International; Investigation; Leaky Gut; Lipopolysaccharides; Liver; Longitudinal Studies; Mucous Membrane; Observational Study; Outcome; Participant; Pathogenesis; Patient Recruitments; Patients; Peripheral Blood Mononuclear Cell; Phase; Phenotype; Plasma; Proviruses; Public Domains; Public Health; RNA; Recombinant DNA; Research; Research Project Grants; Resources; Scientist; T-Lymphocyte; Target Populations; Translational Research; Viral Load result; Virus Integration; Virus Replication; alcohol abstinence; alcohol effect; antiretroviral therapy; chemokine; comorbidity; cytokine; design; follow-up; immune activation; innovation; longitudinal analysis; microbial; novel marker; novel therapeutics; prospective; recruit; repository; treatment response; virology

Abstract Alcohol overconsumption and HIV infection are both major health issues worldwide. Alcohol abuse is more prevalent among HIV-infected people than the general population and strongly associated with poor adherence to antiretroviral therapy (ART) and poor treatment response, leading to HIV progression and ART drug resistance. More drastically, alcohol overconsumption and HIV infection independently damage the gastrointestinal (GI) tract mucosal barrier, leading to a leaky gut that allows microbial translocation (MT) and accumulation of microbial components such as lipopolysaccharide (LPS) in the blood. In HIV patients, MT is a cause of chronic immune activation and inflammation, which is a hallmark of progressive HIV infection and better predicts disease outcome than plasma viral load. We hypothesize that alcohol overconsumption and HIV infection exacerbate MT, immune activation, inflammation, and viral replication, thereby accelerating disease progression of HIV infection and alcoholic liver disease such as alcoholic hepatitis (AH). We also hypothesize that alcohol abstinence slows or reverses immunological and virological impacts in HIV-infected heavy drinkers. We have formed a research team consisting of six scientists with complementary expertise in basic, translational, and clinical research of AH and HIV immunopathogenesis to undertake paradigm-changing investigations in the field of alcohol abuse in HIV patients (Aim 1, UH2 phase). We will enroll HIV-infected heavy drinkers and controls for studying alcohol's impact on HIV-associated comorbidities (Aim 2, UH2 phase). Participants recruited in the UH2 phase will be followed up every 6-month for a year for UH3 phase longitudinal analysis (Aim 3). The UH3 phase will also recruit and follow up new participants to perform a longitudinal analysis of alcohol's impact on MT, immune cell activation, inflammation, and viral replication and integration in HIV-infected heavy drinkers with or without AH (UH3 Phase). Our proposal is highly innovative and will greatly aid in developing novel biomarkers and therapies of HIV-infected heavy drinkers. The biosample repository, upon its placement in the public domain, will become a significant resource for facilitating national and international investigations of alcohol and HIV interactions.

摘要 酒精过度消费和艾滋病毒感染都是全球主要的健康问题。 酗酒在艾滋病毒感染者中比在一般人群中更为普遍， 与抗逆转录病毒治疗（ART）依从性差和治疗效果差密切相关 反应，导致艾滋病毒进展和抗逆转录病毒药物耐药性。更严重的是，酒精 过度消费和HIV感染分别损害胃肠道 粘膜屏障，导致肠道渗漏，允许微生物易位（MT）， 微生物成分如脂多糖（LPS）在血液中的积累。艾滋病毒 在患者中，MT是慢性免疫激活和炎症的原因，这是 进行性HIV感染和更好地预测疾病的结果比血浆病毒载量。我们 假设过度饮酒和艾滋病毒感染会加剧MT、免疫 激活、炎症和病毒复制，从而加速HIV的疾病进展 感染和酒精性肝病，如酒精性肝炎（AH）。我们还假设， 戒酒可减缓或逆转HIV感染者的免疫和病毒学影响 酗酒者我们成立了一个由六名科学家组成的研究小组， 在AH和HIV的基础、转化和临床研究方面的互补专业知识 免疫发病机制进行范式改变调查领域的酒精 艾滋病毒患者的滥用（目标1，UH2阶段）。我们将招募感染艾滋病毒的酗酒者， 对照研究酒精对HIV相关合并症的影响（Aim 2，UH2阶段）。 UH2阶段招募的受试者将每6个月接受一次UH3随访，持续一年 阶段纵向分析（目标3）。UH3阶段还将招募和跟进新的 参与者对酒精对MT，免疫细胞活化， 炎症，以及HIV感染的重度饮酒者中的病毒复制和整合， AH（UH3阶段）。我们的建议是高度创新的，将大大有助于开发新的 HIV感染的酗酒者的生物标志物和治疗。生物样本储存库， 在公共领域的安置，将成为促进国家和 酒精和艾滋病毒相互作用的国际调查。

项目成果

Blood Biomarkers of Intestinal Epithelium Damage Regenerating Islet-derived Protein 3α and Trefoil Factor 3 Are Persistently Elevated in Patients with Alcoholic Hepatitis.

• DOI: 10.1111/acer.14579
• 发表时间: 2021-04
• 期刊: Alcoholism, clinical and experimental research
• 作者: Yang J;Syed F;Xia Y;Sanyal AJ;Shah VH;Chalasani N;Zheng X;Yu Q;Lou Y;Li W
• 通讯作者: Li W

Cell-to-cell transmission of HIV-1 from provirus-activated cells to resting naïve and memory human primary CD4 T cells is highly efficient and requires CD4 and F-actin but not chemokine receptors.

• DOI: 10.1002/jmv.28005
• 发表时间: 2022-11
• 期刊: JOURNAL OF MEDICAL VIROLOGY
• 影响因子: 12.7
• 作者: Lan, Jie;Li, Wei;Yu, Richard;Syed, Fahim;Yu, Qigui
• 通讯作者: Yu, Qigui

The circulating microbiome signature and inferred functional metagenomics in alcoholic hepatitis.

• DOI: 10.1002/hep.29623
• 发表时间: 2018-04
• 期刊: Hepatology (Baltimore, Md.)
• 作者: Puri P;Liangpunsakul S;Christensen JE;Shah VH;Kamath PS;Gores GJ;Walker S;Comerford M;Katz B;Borst A;Yu Q;Kumar DP;Mirshahi F;Radaeva S;Chalasani NP;Crabb DW;Sanyal AJ;TREAT Consortium
• 通讯作者: TREAT Consortium

PD-L1 signaling in reactive astrocytes counteracts neuroinflammation and ameliorates neuronal damage after traumatic brain injury.

• DOI: 10.1186/s12974-022-02398-x
• 发表时间: 2022-02-08
• 期刊: Journal of neuroinflammation
• 影响因子: 9.3
• 作者: Gao X;Li W;Syed F;Yuan F;Li P;Yu Q
• 通讯作者: Yu Q