Novel viruses and viral dynamics in multiple transfusion recipients

多次输血受者中的新型病毒和病毒动态

• 批准号: 9251876
• 负责人: Amit Kapoor
• 金额: $ 38.16万
• 依托单位: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9251876
• 关键词: Agammaglobulinemia; Astroviridae; Astrovirus; Bioinformatics; Biological Assay; Biometry; Blood; Blood Coagulation Factor; Blood Transfusion; Blood donor; Blood specimen; Cardiovirus; Chronic; Circoviridae; Circovirus; Classification; Clinical; Clinical Data; Data; Disease; Evolution; Family Picornaviridae; Fever; General Population; Genetic; Genetic Variation; Genome; Genomics; Genotype; Goals; HIV; HIV/HCV; Health; Hemophilia A; Hepatitis; Hepatitis B; High Prevalence; High-Throughput Nucleotide Sequencing; Human; Human Parvovirus B19; Immunoprecipitation; Individual; Infection; Interruption; Knowledge; Longitudinal Studies; Luciferases; Lung diseases; Molecular; Multicenter Hemophilia Cohort Study; Parvoviridae; Parvovirus; Patients; Plasma; Population; Population Dynamics; Prevalence; Reporting; Risk; Sampling; Secondary to; Sequence Analysis; Serologic tests; Serological; Seroprevalences; Serum; Sickle Cell Anemia; Study Subject; Symptoms; System; Testing; Thalassemia; Time; Transfusion; Transfusion-Transmitted Virus; Transplant Recipients; Trauma patient; Tymoviridae; Tymovirus; United States; Viral; Virus; Virus Diseases; base; blood product; co-infection; cohort; genome sequencing; high risk; innovation; longitudinal analysis; novel; novel virus; prevent; public health relevance; screening; superinfection; transmission process; virology; virus genetics; virus identification

DESCRIPTION (provided by applicant): Studies to find new-unknown blood borne viruses (BBV) generally focus on individual blood samples of donors or recipients with clinical symptoms (fever, hepatitis, etc.). Patients with hemophilia, sickle cell disease, thalassemia, agammaglobulinemia, transplant recipients and others, require chronic transfusion of blood or blood derived products, often made by pooling samples of 20-60,000 blood donors. Given this fact, we hypothesize that an unbiased high- throughput sequencing (UHTS) based study of a few hundred multiple transfusion recipients (MTR) will enable identification of several new BBV that otherwise can only be found by screening several thousands of individual blood samples. Multicenter Hemophilia Cohort Study (MHCS) subjects received multiple transfusions of coagulation factors made by pooling plasma of thousands of individual donors. Moreover, a majority of MHCS subjects are co-infected with HIV, making them highly susceptible to secondary virus infections; therefore we anticipate that the BBVs that are very rare infections in general population will be common infections in MHCS subjects. To test these hypothesis, we used UHTS (preliminary results) to analyze two samples each of 16 MHCS subjects separated by >4000 days (>10 yrs.). We detected an average of 3.4 and 10.4 different viruses in first and last time point samples, respectively. Evolutionary analyses done using the species specific PCR and clonal sequencing indicated distinct genetic diversity, composition and co-variance of different BBV species over time. Noticeably, in addition to finding high prevalence of HIV, HCV, HBV, GBVc, TTV and Parvovirus B19, we found several recently identified viruses never before reported in human blood samples and several new viruses. Our goal is genetic characterization of these new BBV found in human serum samples, confirm their authentic human infection using serology and determine their infection prevalence in different MTR cohorts, Transfusion Transmitted Virus Study subjects, healthy blood donors and other disease cohorts. Approximately 5 million individuals require transfusion of human blood derived product every year in the United States alone. The proposed identification of new viruses found in human blood, their genetic characterization and prevalence in different population will help in conducting subsequent studies to determine their risk of transfusion transmission and in developing strategies to prevent new infections/diseases.

描述（由申请人提供）：寻找新的未知血源病毒（BBV）的研究通常集中于有临床症状（发烧、肝炎等）的捐献者或接受者的个人血液样本。血友病、镰状细胞病、地中海贫血、丙种球蛋白血症、移植受者等患者需要长期输注血液或血液衍生产品，这些血液或血液衍生产品通常是通过汇集 20-60,000 名献血者的样本制成的。鉴于这一事实，我们假设对数百名多次输血受者 (MTR) 进行基于无偏高通量测序 (UHTS) 的研究将能够识别几种新的 BBV，否则只能通过筛查数千个个体血液样本来发现。多中心血友病队列研究 (MHCS) 受试者接受了多次输注凝血因子，这些凝血因子是通过汇集数千名个体捐献者的血浆而制成的。此外，大多数 MHCS 受试者同时感染 HIV，使他们极易继发病毒感染；因此，我们预计，在普通人群中非常罕见的 BBV 感染将在 MHCS 受试者中成为常见感染。为了检验这些假设，我们使用 UHTS（初步结果）分析了 16 名 MHCS 受试者中每人的两个样本，这些样本间隔时间超过 4000 天（>10 年）。我们在第一个和最后一个时间点样本中平均分别检测到 3.4 种和 10.4 种不同的病毒。使用物种特异性 PCR 和克隆测序进行的进化分析表明，随着时间的推移，不同 BBV 物种具有不同的遗传多样性、组成和协方差。值得注意的是，除了发现 HIV、HCV、HBV、GBVc、TTV 和细小病毒 B19 的高患病率之外，我们还发现了几种最近在人类血液样本中从未报道过的病毒和几种新病毒。我们的目标是对人类血清样本中发现的这些新 BBV 进行基因表征，利用血清学确认其真实的人类感染情况，并确定其在不同 MTR 队列、输血传播病毒研究对象、健康献血者和其他疾病队列中的感染率。仅在美国，每年就有约 500 万人需要输注人类血液衍生产品。拟议对人类血液中发现的新病毒、其遗传特征和在不同人群中的流行情况进行鉴定，将有助于开展后续研究，以确定其输血传播的风险，并制定预防新感染/疾病的策略。