Characterization of plasma virome in people who inject drugs to identify early transmission networks of HIV and other bloodborne infections

注射吸毒者血浆病毒组的特征，以识别艾滋病毒和其他血源性感染的早期传播网络

• 批准号: 10160212
• 负责人: Abraham Kandathil
• 金额: $ 20.47万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-15 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10160212
• 关键词: Acute Hepatitis C; Age; Baltimore; Biometry; Blood; Centers for Disease Control and Prevention (U.S.); Circular DNA; Communicable Diseases; Communities; Complementary DNA; Country; County; Coupled; Data; Deltastab; Detection; Diagnosis; Disease Outbreaks; Disincentive; Drug usage; Early identification; Epidemic; Epidemiology; Foundations; Gender; Goals; HIV; HIV Infections; HIV/HCV; Haplotypes; Health; Hepatitis C; Hepatitis C Acquisition; Hepatitis C Transmission; Hepatitis C virus; Human; Illicit Drugs; Infection; Injecting drug user; International; Interruption; Knowledge; Link; Mathematics; Methods; Modeling; Molecular; Opioid; Outcome; Pathogenicity; Patient Self-Report; Performance; Persons; Phylogenetic Analysis; Plasma; Population Surveillance; Prevention strategy; Probability; RNA; Research; Research Personnel; Risk; Sampling; San Francisco; Sensitivity and Specificity; Serology; Source; Stigmatization; Symptoms; System; Techniques; Testing; Time; Transfusion-Transmitted Virus; Uncertainty; United States; Viral; Virus; Virus Diseases; Work; base; bioinformatics tool; co-infection; cohort; combat; disease transmission; experimental study; follow-up; high risk; improved; injection drug use; innovation; insight; interest; intravenous injection; member; nanopore; next generation sequencing; novel; novel strategies; opioid epidemic; pathogen; pathogen genome; pathogenic virus; programs; rural counties; seroconversion; superinfection; tertiary prevention; tool; transmission process; viral detection; virome

There is an urgent need for implementing innovative methods to combat the resurgence of HIV and hepatitis C virus (HCV) infection among people who inject drugs (PWID). The opioid epidemic in the United States threatens to undermine national 2030 elimination goals for both viruses. While tertiary prevention strategies have facilitated to a certain extent in improving health outcomes it has been difficult to interdict transmission of infectious diseases. Moreover, bloodborne infections like HIV and HCV have no symptoms on initial infection, and thus the beginning of an epidemic can predate the recognition of the first diagnosed case in the community. In addition, surveillance is also hindered by disincentives for “self-report” caused by stigmatization and criminalization. We propose using plasma virome components shared between subjects due to intravenous injection of illicit drugs for early identification of transmission networks in PWID. Transmission studies have shown that HCV precedes HIV infection in PWID, and hence new HCV infections serve as strong predictors of communities at risk for HIV. We now ask if there are virome components that are shared before HCV transmission in PWID. Our hypothesis is that viruses of unknown pathogenicity will accumulate in blood before HIV or HCV infection and that they will be transmitted by injection drug use such that their sequences reveal those epidemiological linkages. We will first confirm our preliminary observations made in our Baltimore cohort using molecular and serology assessments in another PWID cohort from San Francisco. Like the Baltimore cohort, the San Francisco cohort allows access to plasma samples before, during, and after acquisition of HCV infection. We will compare plasma virome between age and gender matched twenty HCV positive (HCV+PWID) and twenty HCV negative (HCV-PWID) PWID. Plasma from two time points covering the same duration of follow up between the two groups will be tested. The HCV+PWID will be tested before and during acquisition of HCV. Differences will be determined by enumerating viral infections between the groups at both time points. The plasma virome will then be characterized further by NGS using Oxford Nanopore after viral target enrichment. The long reads allow identification of viral strains (haplotype) suitable for phylogenetic studies. We will characterize the plasma virome in subjects from the Baltimore cohort (n=10) known to share (linked) HCV sequences. In addition, we will sequence the same subjects before HCV acquisition to identify shared (linked) virome sequences before HCV acquisition. Similar sequence characterization of plasma samples from the San Francisco cohort (n=10) will also be done at two time points. Sequencing both cohorts further validates the approach since no sequence sharing (linkage) of the virome components should be observed between the two cohorts. By using routinely collected samples, this work could transform the research of drug use networks and change public health surveillance of HIV, HCV, and expose occult dynamics of reinfection and superinfection.

迫切需要实施创新方法来对抗艾滋病毒的死灰复燃 注射吸毒者 (PWID) 中的丙型肝炎病毒 (HCV) 感染。美国的阿片类药物流行 各国威胁要破坏 2030 年消除这两种病毒的国家目标。三级预防的同时 战略在一定程度上促进了健康结果的改善，但很难阻止 传染病的传播。此外，HIV 和 HCV 等血源性感染在患者身上没有任何症状。 初次感染，因此流行病的开始可能早于首例确诊病例的发现 在社区中。此外，监督也因“自我报告”的抑制因素而受到阻碍。 污名化和刑事定罪。我们建议使用受试者之间共享的血浆病毒组成分，因为 静脉注射非法药物，以便及早识别吸毒者的传播网络。 传播研究表明，吸毒者中丙型肝炎病毒先于艾滋病毒感染，因此出现了新的丙型肝炎病毒 感染是存在艾滋病毒风险的社区的有力预测因素。我们现在询问是否有病毒体 PWID 中 HCV 传播之前共享的组件。我们的假设是未知的病毒 HIV或HCV感染前，致病性会在血液中积聚，并通过注射传播 药物使用，使得它们的序列揭示了这些流行病学联系。我们首先会确认我们的初步 使用另一个吸毒者队列的分子和血清学评估在我们的巴尔的摩队列中进行的观察 来自旧金山。与巴尔的摩队列一样，旧金山队列允许获取血浆样本 在感染 HCV 之前、期间和之后。我们将比较年龄和年龄之间的血浆病毒组 性别匹配 20 名 HCV 阳性 (HCV+PWID) 和 20 名 HCV 阴性 (HCV-PWID) PWID。等离子体 从覆盖相同持续时间的两个时间点对两组之间的随访进行测试。这 HCV+PWID 将在 HCV 采集前和采集过程中进行测试。差异将由以下因素确定 计算两个时间点各组之间的病毒感染情况。然后血浆病毒组将被 在病毒靶标富集后，使用 Oxford Nanopore 通过 NGS 进一步表征。长读允许 鉴定适合系统发育研究的病毒株（单倍型）。我们将表征等离子体 巴尔的摩队列 (n=10) 受试者的病毒组已知共享（相关）HCV 序列。此外，我们 将在 HCV 采集前对相同受试者进行测序，以识别共享（相关）病毒组序列 丙肝病毒获取。旧金山队列血浆样本的相似序列特征 (n=10) 也将在两个时间点进行。对两个队列进行测序进一步验证了该方法，因为没有 应观察两个队列之间病毒组成分的序列共享（连锁）。 通过使用常规收集的样本，这项工作可以改变吸毒网络的研究 改变对艾滋病毒、丙型肝炎病毒的公共卫生监测，并揭露再感染和重复感染的隐秘动态。