UChicago Medicine biobank helps peg new human virus

Physicians Andrew Aronsohn, MD, Assistant Professor of Medicine (left) and Donald M. Jensen, MD, Professor of Medicine, Director, Center for Liver Diseases. (Photo by Shahzad Ahsan)

Physicians Andrew Aronsohn, MD, Assistant Professor of Medicine (left) and Donald M. Jensen, MD, retired Professor of Medicine and former director, Center for Liver Diseases. (Photo by Shahzad Ahsan)

On Dec. 11, 2015, a team of scientists reported the discovery of a new human virus, now known as human pegivirus-2 (HPgV-2).

In the journal PLOS Pathogens, the researchers—from Abbott, the University of California San Francisco (UCSF) and the Center for Liver Diseases at the University of Chicago—described eight complete and four partial strains of the previously unknown virus.

“Based on our findings, our team used the genetic makeup of the virus to develop both a molecular test for detecting it in the bloodstream and an antibody test for determining an immune response to the virus,” said John Hackett Jr, PhD, divisional vice president of applied research and technology at Abbott. “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.”

The researchers showed that infection with this blood-borne virus is tightly linked with hepatitis C. All 12 patients in the study who carried HPgV-2 were also infected with hepatitis C. It is unclear, however, whether the virus can cause disease on its own.

“We are just beginning to explore the clinical ramifications,” said study co-author Andrew Aronsohn, MD, a liver specialist and assistant professor of medicine at the University of Chicago. “Does it make a difference to the infected person’s health? Does it work with hepatitis C to make patients even sicker? We don’t yet know. We only know that a blood-borne virus, never before detected, is out there.”

The first evidence came from a former University of Chicago Medicine patient. The “index case” was a 70-year-old woman with multiple complex health issues, as well as HPgV-2. She died from multi-organ failure in 2011.

Luckily—for the researchers—she had agreed to donate a little bit of her blood during a previous hospital stay in 2008. The blood was stored in TRIDOM, short for Translational Research Initiative in the Department of Medicine, a human tissue biobank established at the university in 2005. TRIDOM now holds blood samples from more than 7,000 patients. Investigators use the collection to search for connections, like this one, between clinical information and various biological markers.

Dr. Aronsohn was kind enough to answer some questions about the process of the team’s discovery.

ScienceLife: You and colleagues at Abbott and UCSF found this virus in blood from 12 patients. How common do you think the virus might be?

Andrew Aronsohn: We found evidence of the virus in 12 of the 2,440 patients who had their blood screened, so it’s not very common. That’s 12 out of 982 people with hepatitis C, and zero out of 1,458 people who did not have hepatitis C. There are far more people without hepatitis C, thank goodness, than with; so overall it’s a fraction of one percent. There was no evidence of active HPgV-2 infection in patients with HIV or hepatitis B, or in healthy volunteer blood donors.

SL: How do we think patient #1 acquired this virus?

AA: We don’t know specifically. Her history, however, put her at high risk for blood-borne infections. She suffered from sickle-cell disease and hypertension. She had liver damage from hepatitis C plus kidney disease. She was diagnosed with hepatitis in 1999 and treated, unsuccessfully, with interferon. Because of her sickle-cell disease, she had frequent blood transfusions throughout her lifetime. That raised her risk for such infections.

Did this virus affect her health?

It’s hard to know. This was not someone who picked up a virus and immediately dies from the infection. She was very sick, had been sick for a long time, with a lot of co-morbidities. We are looking for more samples, more cases, to try to understand the impact of this virus on patients with hepatitis C. But it will be difficult to pick apart the damage caused by hepatitis C from the as yet unknown risks of human pegivirus-2. Several recent reports suggest it may even be helpful. In patients with HIV, co-infection with HPgV-1 may delay progression to AIDS. Co-infection with HPgV-1 has also been associated with improved survival in patients with Ebola.

What is a pegivirus?

Pegivirus is the name for a genus of RNA viruses. The “Pe” suggests it’s persistent and “G” refers to its former name: hepatitis G, which is now called human pegivirus-1. It was discovered in 1995. The abbreviation HPgV-2, obviously, stands for human pegivirus-2. There are also animal pegiviruses that can infect bats, rodents, horses, chimpanzees and others.

How was HPgV-2 discovered?

We screened blood from 169 current and former patients with chronic liver disease to identify potential new infections. Samples that looked promising were sent to UCSF. In the sample rom patient 1, they identified two contiguous sequences that shared 60 percent identity to a simian pegivirus. They were subsequently able to close the gaps and recover a nearly complete draft genome. To confirm that, we sent plasma from that same patient to Abbott Laboratories. They independently went through the same process and assembled a genome that was 99.73 identical to the UCSF version. The team named it pegivirus-2. The first strain is UC0125.US.

You found 12 strains.  How similar were they?

The team eventually found 8 full genomes that were quite similar, plus four more partial genomes. HPgV-2 was quite different from HPgV-1. Three of the 12 patients had both pegiviruses, 1 and 2, as well as hepatitis C.

How important was TRIDOM in the discovery process?

That’s where the project first got traction. Having that infrastructure in place, with thousands of samples acquired from patients with complete medical records who had already given consent, made it much easier. It is a large collection, so we had to develop very specific search criteria to find just what we were hoping for without getting overwhelmed by thousands of samples. I should add, we got super lucky.

What are the next steps?

I’ll defer to the corresponding author Charles Chiu, MD, PhD, director of UCSF-Abbott Viral Diagnostics and Discovery Center, who summed it up thus: Our study “offers a first look at the evolution and diversity of this virus.” Discoveries like this, he added, “provide us with information to push the boundaries of scientific knowledge and understanding.”

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NIH grant R01-HL105704 and a UCSF-Abbott Pathogen Diagnostics and Discovery Award funded the study, “Discovery of a Novel Human Pegivirus in Blood Associated with Hepatitis C Virus Co-Infection, doi:10.1371/journal.ppat.1005325. Additional authors were Donald M. Jensen from UChicago; Michael G. Berg, Kelly Coller, Matthew Frankel, Kevin Cheng, Kenn Forberg, Marilee Marcinkus, George Dawson and Catherine Brennan from Abbott; and Deanna Lee and Samia N. Naccache from UCSF.

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