Frog cells offer clues to targetable ‘escape hatch’ for hepatitis E virus

Cells from the African clawed frog help explain how hepatitis E virus particles spread throughout the body.

Hepatitis E is a liver virus that causes 20 million infections a year, mostly in East and South Asia, according to the World Health Organization (WHO). The virus is primarily spread through contaminated food and water, but lately it’s been on the rise in Europe, where it’s believed to be caused by the consumption of undercooked meat.

There is no therapy that specifically attacks the E strain of the virus, but now researchers led by Princeton have found a clue that could lead to a targeted treatment.

The research team discovered that when hepatitis E infects cells, it makes “viroporins,” or proteins that create holes in the cell membrane allowing the virus to escape and spread, according to a release from Princeton. Drugs that disrupt viroporin production have already been developed for other viruses, including HIV and hepatitis C.

Whitepaper Download

Reducing the Complexity and Costs of Channel Planning and Logistics

How can you make the process of bringing your product to market less complex while also reducing costs? This Whitepaper identifies opportunities to simplify channel strategies for biopharma companies, their customers and patients. Discover how you can deliver savings and innovation to your business.

The key to targeting viroporin production is to figure out how the virus is learning to make the destructive proteins. In the case of hepatitis E, the Princeton researchers found that a section of the virus’ RNA called open reading frame 3 (ORF3) contains the instructions it needs to make viroporins. The research was published in the Proceedings of the National Academy of Sciences.

To prove ORF3 is the key to producing an escape route for hepatitis E particles, the scientists worked with researchers at Rutgers New Jersey Medical School on a model using cells from the African clawed frog. By measuring electric currents, they discovered that ORF3 RNA acts as an “ion channel,” disrupting the cells’ physiology to the point where virus particles could slip through and infect other cells.

Hepatitis E produces only mild symptoms in healthy people, but it is dangerous for people with compromised immune systems and women in the late stages of pregnancy, according to WHO. A vaccine has been developed but is only available in China.

The next step for the Princeton-led team is to find points along the ORF3 pathway that might be able to be targeted with drugs.

"We are working on identifying parts of the protein that could possibly prevent the formation of the ion channel or prevent the flux of ions through the channel," said Alexander Ploss, a Princeton assistant professor of molecular biology and the senior author of the study, in the release.

Suggested Articles

The clinical testing giant LabCorp will now begin rolling out a blood test for lung cancer developed by Resolution Bioscience.

Silverback Therapeutics reeled in $85 million to advance its lead antibody-drug conjugate through the clinic and develop its earlier-stage pipeline.

Cognoa aims to equip pediatricians with an AI-powered app that can spot the signs of autism, allowing them to diagnose in the doctor's office.