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: 8697351
• 负责人: Amit Kapoor
• 金额: $ 41.99万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-05 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8697351
• 关键词: African Swine Fever-Like Viruses; Agammaglobulinemia; Astrovirus; Bioinformatics; Biological Assay; Blood; Blood Coagulation Factor; Blood Transfusion; Blood donor; Blood specimen; Cardiovirus; Chronic; Circovirus; Classification; Clinical; Clinical Data; Data; Disease; Evolution; Family Picornaviridae; Fever; General Population; Genetic; Genetic Variation; Genome; Genomics; Genotype; Goals; HIV; Health; Hemophilia A; Hepatitis; Hepatitis B Virus; Hepatitis C virus; High Prevalence; High-Throughput Nucleotide Sequencing; Housing; Human; Human Parvovirus B19; Immunoprecipitation; Individual; Infection; Knowledge; Longitudinal Studies; Luciferases; Lung diseases; Molecular; Multicenter Hemophilia Cohort Study; Parvovirus; Patients; Plasma; Population; Population Dynamics; Prevalence; Reading; 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; Tymovirus; United States; Viral; Virus; Virus Diseases; base; blood product; cohort; genome sequencing; high risk; innovation; novel; novel virus; prevent; public health relevance; screening; transmission process; 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）：研究发现新的血液传播病毒（BBV）通常集中于供体供体的单个血液样本或患有临床症状的接受者（发烧，肝炎等）。血友病，镰状细胞疾病，地中海贫血，agammagloblobloblinemia，移植受者和其他患者需要长期对血液或血液衍生产物的慢性输血，通常是通过汇总20-60,000名献血者的样本来制作的。鉴于这一事实，我们假设基于几百个多个输血接受者（MTR）的公正高吞吐量测序（UHT）研究将能够鉴定几个新的BBV，否则只能通过筛查数千种单个血液样本来找到这些新的BBV。多中心血友病队列研究（MHC）受试者通过合并数千个单个捐助者的血浆来接受多种凝血因子的输血。此外，大多数MHC受试者均与HIV共同感染，使其非常容易受到继发性病毒感染的影响。因此，我们预计普通人群中非常罕见的感染的BBV将是MHCS受试者的常见感染。为了检验这些假设，我们使用UHT（初步结果）分析了16个MHCS受试者中的两个样本，分别为4000天（> 10年）。我们在第一个和最后一个时间点样品中平均检测到3.4和10.4不同的病毒。使用特异性PCR和克隆测序进行的进化分析表明，随着时间的流逝，不同BBV物种的遗传多样性，组成和共同变化。明显的是，除了发现HIV，HCV，HBV，GBVC，TTV和小男病毒B19的较高流行率外，我们还发现了几种最近在人类血液样本和几种新病毒中从未报道过的最近鉴定出的病毒。我们的目标是在人血清样品中发现的这些新BBV的遗传表征，使用血清学证实其真实的人类感染，并确定它们在不同的MTR同伴中的感染率，输血传播的病毒研究对象，健康的血液供体和其他疾病群体。仅在美国，大约有500万个人需要每年人类血液衍生的产物输血。提出的对人类血液中发现的新病毒的鉴定，它们在不同人群中的遗传特征和患病率将有助于进行随后的研究，以确定其输血传播的风险以及制定防止新感染/疾病的策略。