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Sequencing Study IDs Human Pegivirus in Individuals With Hepatitis C

NEW YORK (GenomeWeb) – A team led by investigators at the University of California, San Francisco-Abbott Viral Diagnostics and Discovery Center has identified a new humans pegivirus in a subset of individuals infected with hepatitis C virus (HCV).

As they reported in PLOS Pathogens, the researchers did metagenomic sequencing on blood samples from more than 150 individuals with chronic liver disease, identifying a handful of reads corresponding to human pegivirus 2, or HPgV-2, in an individual who had been infected with HCV and died from sepsis.

Using new diagnostic assays aimed at the virus, the team screened thousands more blood samples, turning up 11 more HPgV-2-postive samples, all from individuals with HCV. Along with an analysis of complete or partial genome sequences for the viruses, the group characterized the patients' antibody responses to the HPgV-2 to start unraveling its transmission patterns and potential consequences for infected individuals.

"Our next step is to explore whether this new virus can cause disease, and if so, work with blood banks to continue to help safeguard the world's blood supply against these types of new viruses," co-author John Hackett, Jr., vice president of applied research and technology at Abbott Laboratories, said in a statement.

The HPgV-2 that Hackett and his colleagues identified in the first of the HCV patients was roughly 96 percent identical to a human pegivirus described in mBio by researchers from Columbia University and elsewhere. That virus, dubbed human hepegivirus 1 (HHPgV-1), was identified in blood transfusion recipients in the US or Europe.

Meanwhile, studies going back a decade hinted at the presence of an apparently non-pathogenic human pegivirus — known as HPgV-1 or GBV-C — in blood samples from some hepatitis patients.

With that in mind, Chiu and colleagues did metagenomic sequencing on blood samples from 169 individuals who had been treated for chronic liver disease at the University of Chicago Medical Center.

With the help of a bioinformatics pipeline focused on pathogen detection, they narrowed in on HPgV-2 reads in the index patient, a deceased 70 year-old woman with a history of sickle cell disease, HCV infection, and kidney problems.

Through deeper Illumina sequencing coupled with Sanger sequencing, the team put together an almost 9,900 base draft genome assembly for HPgV-2, which appeared to be distantly related to pegiviruses found in bat and rodent hosts.

Additional metagenomic sequencing on another blood sample from the same individual confirmed the HPgV-2 infection and produced reads that the researchers used to assemble an independent HPgV-2 genome assembly that was nearly identical to the original draft sequence.

To get a sense of how widespread HPgV-2 infection might be, they used a combination of multiplex RT-PCR and serological assays to screen thousands more blood samples from individuals with or without HCV, HIV, and/or hepatitis B virus infection.

In the process, the team narrowed in on 11 samples with HPgV-2 RNA. All of the infected individuals also had HCV. On the other hand, the new pegivirus did not turn up in almost 1,500 screened samples from virus-free individuals nor in almost 500 individuals infected with HIV alone.

Based on complete genomes for eight of the HPgV-2 isolates and partial genome sequences for four more, the researchers saw some 93 to 94 percent identity between the HPgV-2 strains identified in the study.

Finally, although HPgV-2 infection was only identified in those with HCV, the study's authors did see some HCV-free individuals with apparent antibodies to the virus, hinting that they may have successfully cleared the virus.

Such findings suggest HCV co-infection contribute to HPgV-2 persistence, they speculated, though further research is needed to explore the prevalence and pathogenic potential of HPgV-2.