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: 10406159
• 负责人: Abraham Kandathil
• 金额: $ 24.56万
• 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 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10406159
• 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; Elderly; 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.

迫切需要采取创新方法，防止艾滋病毒的死灰复燃， 丙型肝炎病毒（HCV）感染的人谁注射毒品（PWID）。阿片类药物在美国的流行 各国威胁要破坏国家2030年消除这两种病毒的目标。虽然三级预防 战略在一定程度上促进了健康成果的改善， 传染病的传播。此外，血液传播的感染，如艾滋病毒和丙型肝炎病毒没有症状， 初始感染，因此流行病的开始可以早于第一个诊断病例的识别 在社区此外，监督也受到“自我报告”的抑制因素的阻碍， 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， 静脉注射非法药物，以早期识别PWID的传播网络。 传播研究表明，在PWID中，HCV先于HIV感染，因此新的HCV 感染是艾滋病毒风险社区的有力预测指标。我们现在要问的是， 在PWID中HCV传播前共享的组分。我们的假设是未知的病毒 在感染HIV或HCV之前，致病性会在血液中积累，并通过注射传播 药物使用，以便它们的序列揭示这些流行病学联系。我们将首先确认我们的初步 在我们的巴尔的摩队列中使用另一个PWID队列的分子和血清学评估进行观察 来自旧金山弗朗西斯科。与巴尔的摩队列一样，旧金山弗朗西斯科队列允许获得血浆样本 在获得HCV感染之前、期间和之后。我们将比较不同年龄和性别的血浆病毒组， 性别匹配的20例HCV阳性（HCV+PWID）和20例HCV阴性（HCV-PWID）PWID。血浆 将对两组之间覆盖相同随访持续时间的两个时间点进行检测。的 将在采集HCV之前和期间检测HCV+PWID。差异将由 在两个时间点计数组间的病毒感染。然后血浆病毒组将是 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）。我们将描述等离子体 来自巴尔的摩队列（n=10）的受试者中已知共有（连锁）HCV序列的病毒组。另外我们 将在获得HCV之前对相同的受试者进行测序，以在获得HCV之前鉴定共享的（链接的）病毒组序列。 HCV感染。来自San弗朗西斯科队列（n=10）的血浆样本的相似序列表征 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 在两个组群之间应观察到病毒组组分的序列共享（连锁）。 通过使用常规收集的样本，这项工作可以改变对毒品使用网络的研究， 改变对HIV、HCV的公共卫生监测，暴露再感染和重复感染的隐匿动态。

项目成果

Plasma virome and the risk of blood-borne infection in persons with substance use disorder.

• DOI: 10.1038/s41467-021-26980-8
• 发表时间: 2021-11-25
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Kandathil AJ;Cox AL;Page K;Mohr D;Razaghi R;Ghanem KG;Tuddenham SA;Hsieh YH;Evans JL;Coller KE;Timp W;Celentano DD;Ray SC;Thomas DL
• 通讯作者: Thomas DL