Kandathil Abraham J, Breitwieser Florian P, Sachithanandham Jaiprasath, Robinson Matthew, Mehta Shruti H, Timp Winston, Salzberg Steven L, Thomas David L, Balagopal Ashwin
From Johns Hopkins University and Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Ann Intern Med. 2017 Jul 4;167(1):1-7. doi: 10.7326/M17-0085. Epub 2017 Jun 6.
Next-generation metagenomic sequencing (NGMS) has opened new frontiers in microbial discovery but has been clinically characterized in only a few settings.
To explore the plasma virome of persons who inject drugs and to characterize the sensitivity and accuracy of NGMS compared with quantitative clinical standards.
Longitudinal and cross-sectional studies.
A clinical trial (ClinicalTrials.gov: NCT01285050) and a well-characterized cohort study of persons who have injected drugs.
Persons co-infected with hepatitis C virus (HCV) and HIV.
Viral nucleic acid in plasma by NGMS and quantitative polymerase chain reaction (PCR).
Next-generation metagenomic sequencing generated a total of 600 million reads, which included the expected HIV and HCV RNA sequences. HIV and HCV reads were consistently identified only when samples contained more than 10 000 copies/mL or IU/mL, respectively, as determined by quantitative PCR. A novel RNA virus, human hepegivirus-1 (HHpgV-1), was also detected by NGMS in 4 samples from 2 persons in the clinical trial. Through use of a quantitative PCR assay for HHpgV-1, infection was also detected in 17 (10.9%) of 156 members of a cohort of persons who injected drugs. In these persons, HHpgV-1 viremia persisted for a median of at least 4538 days and was associated with detection of other bloodborne viruses, such as HCV RNA and SEN virus D.
The medical importance of HHpgV-1 infection is unknown.
Although NGMS is insensitive for detection of viruses with relatively low plasma nucleic acid concentrations, it may have broad potential for discovery of new viral infections of possible medical importance, such as HHpgV-1.
National Institutes of Health.
新一代宏基因组测序（NGMS）在微生物发现方面开辟了新领域，但仅在少数情况下进行了临床特征分析。
探索注射毒品者的血浆病毒组，并与定量临床标准相比，对NGMS的敏感性和准确性进行特征分析。
纵向和横断面研究。
一项临床试验（ClinicalTrials.gov：NCT01285050）以及一项对注射毒品者进行的特征明确的队列研究。
丙型肝炎病毒（HCV）和人类免疫缺陷病毒（HIV）合并感染的患者。
通过NGMS和定量聚合酶链反应（PCR）检测血浆中的病毒核酸。
新一代宏基因组测序共产生了6亿条读数，其中包括预期的HIV和HCV RNA序列。通过定量PCR测定，仅当样本分别含有超过10000拷贝/毫升或国际单位/毫升时，才能一致鉴定出HIV和HCV读数。在临床试验中，从2名患者的4份样本中，NGMS还检测到一种新型RNA病毒，即人类庚型肝炎病毒-1（HHpgV-1）。通过使用针对HHpgV-1的定量PCR检测方法，在一个注射毒品者队列的156名成员中，也有17名（10.9%）检测到感染。在这些人中，HHpgV-1病毒血症持续的中位数至少为4538天，并且与检测到其他血源病毒有关，如HCV RNA和SEN病毒D。
HHpgV-1感染的医学重要性尚不清楚。
尽管NGMS对检测血浆核酸浓度相对较低的病毒不敏感，但它可能在发现具有潜在医学重要性的新病毒感染方面具有广泛潜力，如HHpgV-1。
美国国立卫生研究院。
