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Next-generation metagenomic sequencing may detect viral infections

Next-generation metagenomic sequencing, or NGMS, can potentially detect new viral infections in the blood that may be of medical importance, such as human hepegivirus-1, according to data published in Annals of Internal Medicine.

“In clinical practice, NGMS has been used to detect unsuspected pathogens, and it is also being used to characterize the composition of complex populations of recognized viruses, such as HIV-1 and hepatitis C virus (HCV),” Abraham J. Kandathil, PhD, assistant professor of medicine at Johns Hopkins University, and colleagues wrote. “Although NGMS can uncover novel sequences the limits of detection are not clearly defined... Likewise, although NGMS provides a means to estimate the quantity of microbial species in a sample, it is not clear how those measurements compare with well-established clinical laboratory quantitative standards.”

Researchers analyzed the plasma virome of people co-infected with HCV and HIV who inject drugs, and evaluated the sensitivity and accuracy of NGMS compared with quantitative clinical standards. They used plasma samples taken before interferon treatment and corresponding samples collected at 72 or 168 hours after interferon administration from individuals enrolled in a prospective clinical trial. Using NGMS and quantitative PCR, they measured the viral nucleic acid in plasma.

Including the expected HIV and HCV RNA sequences, NGMS generated 600 million reads. The NGMS only consistently identified HIV and HCV reads when samples contained more than 10,000 copies/mL or IU/mL, respectively, as determined by quantitative PCR. However, NGMS detected a novel RNA virus, known as human hepegivirus-1 (HHpgV-1), in four samples from two individuals. In addition, using a quantitative PCR test for HHpgV-1 showed infection in 17 of 156 (10.9%) members in a cohort of persons who injected drugs. In these same individuals, HHpgV-1 viremia persisted for a median of at least 4,538 days and was linked to discovery of other bloodborne viruses including HCV and SEN virus D (SENV-D).

“We found high prevalence of a newly described human hepegivirus that may be associated with ongoing HCV and SENV-D infection and may also provide novel insights into the sensitivity and accuracy of NGMS for quantification of viral RNA in human blood,” Kandathil and colleagues wrote. “Additional work is needed to further characterize the clinical importance of such newly discovered members of the human virome and to optimize the performance and application of NGMS.” – by Savannah Demko

Disclosures: Kandathil reports a grant from the NIH. Please see the full study for a complete list of all other authors’ relevant financial disclosures.