Nav: Home

Findings could lead to treatment of hepatitis B

June 04, 2018

Researchers at the University of Delaware, working with colleagues at Indiana University, have gained new insights into the virus that causes hepatitis B -- a life-threatening and incurable infection that afflicts more than 250 million people worldwide.

The discovery, which was published April 27 in the journal eLife, reveals previously unknown details about the capsid, or protein shell, that encloses the virus' genetic blueprint.

Scientists believe that the capsid, which drives the delivery of that blueprint to infect a host cell, is a key target in developing drugs to treat hepatitis B.

"With hepatitis B, the structure of the capsid has been known for years, but we wanted to study its motion and its influence on its surroundings," said Jodi A. Hadden, an independent postdoctoral researcher in UD's Department of Chemistry and Biochemistry and the lead author of the new paper.

Jodi Hadden and Juan Perilla have used computer simulations to learn more about the capsid, or protein shell, that encloses the genetic blueprint of the hepatitis B virus. An image of the capsid shows how it is made up of 240 proteins.

Hadden and the research team used supercomputing resources to perform what are known as all-atom molecular dynamics simulations.

Molecular dynamics simulations allow researchers to study the way molecules move in order to learn how they carry out their functions in nature. Computer simulations are the only method that can reveal the motion of molecular systems down to the atomic level and are sometimes referred to as the "computational microscope."

In the case of the simulations of the hepatitis B virus, the researchers found that the capsid is not rigid as previously thought, but is highly flexible. They also learned that it can distort into an asymmetric shape, which might allow it to squeeze through an opening into the nucleus of a cell the virus is infecting.

"We think that the capsid might need that ability to distort in order to correctly package its genetic blueprint and get it into the nucleus to generate new copies of the virus during the infection process," Hadden said.

Previous research has used experimental microscopes to study the capsid, which is made up of 240 proteins, but that work hasn't yielded high-resolution images of the complex structure, said Juan R. Perilla, assistant professor of chemistry and biochemistry and a co-author of the new paper.

"It seems clear that the flexibility of the [hepatitis B] capsid is a limiting factor" in the effectiveness of microscopy, he said.

By contrast, the simulations have been able to reveal a more complete picture of the capsid and how it moves, distorts and interacts with its environment, Hadden said. Each simulation involves six million atoms.

"We have all the details down to the atomic level," she said. "You need that to develop a complete understanding of the molecule and to study drug interactions."

The researchers also found that small triangular openings, or pores, in the capsid surface are likely the location where its protein "tails" poke through, sending a signal that is essential to the infection process.

"We know that the capsid tails have to be exposed to the surface at some time for the capsid to travel to the cell nucleus," Hadden said. "It's like hailing a taxi."

All the findings have the potential to lead to drug treatments, she said. For example, if the capsid could be made rigid and unable to distort or if a way could be found to block the triangular pores in its surface, the infection process might be halted.

There's an effective vaccine to prevent hepatitis B, but no cure once a person is infected. The virus causes severe liver disease, which can lead to potentially fatal conditions such as cirrhosis and liver cancer.
-end-


University of Delaware

Related Hepatitis Articles:

Nanotechnology delivers hepatitis B vaccine
X-ray imaging shows that nanostructured silica acts as a protective vehicle to deliver intact antigen to the intestine so that it can trigger an immune response.
Checkmate for hepatitis B viruses in the liver
Researchers at Helmholtz Zentrum München and the Technical University of Munich, working in collaboration with researchers at the University Medical Center Hamburg-Eppendorf and the University Hospital Heidelberg, have for the first time succeeded in conquering a chronic infection with the hepatitis B virus in a mouse model.
How common is Hepatitis C infection in each US state?
Hepatitis C virus infection is a major cause of illness and death in the United States and injection drug use is likely fueling many new cases.
New strains of hepatitis C found in Africa
The largest population study of hepatitis C in Africa has found three new strains of the virus circulating in the general population in sub-Saharan Africa.
High stability of the hepatitis B virus
At room temperature, hepatitis B viruses (HBV) remain contagious for several weeks and they are even able to withstand temperatures of four degrees centigrade over the span of nine months.
Findings could lead to treatment of hepatitis B
Researchers have gained new insights into the virus that causes hepatitis B -- a life-threatening and incurable infection that afflicts more than 250 million people worldwide.
How to cure more hepatitis C patients
The cost of cures for hepatitis C have been prohibitive, but experts who served on an NAS panel have a solution that will save more patients and incentivize drug innovation.
Hepatitis C: A novel point-of-care assay
One of the major challenges identified by the WHO in efforts to eradicate the hepatitis C virus is the diagnosis of chronic cases that are generally asymptomatic.
Countries risk 'running out' of hepatitis C patients to treat, says World Hepatitis Alliance
The latest data on the global hepatitis C epidemic, released today at the World Hepatitis Summit in Sao Paulo, Brazil, reveal that most countries (especially high-income countries) are running out of patients to treat because of the low diagnosis rates worldwide.
Australia currently on track to eliminate hepatitis C by 2030, but challenges remain for hepatitis B
New data released at this year's World Hepatitis Summit in Sao Paulo, Brazil, shows that Australia is currently on track to eliminate hepatitis C thanks to its huge efforts to enable population-wide access to treatment.
More Hepatitis News and Hepatitis Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#540 Specialize? Or Generalize?
Ever been called a "jack of all trades, master of none"? The world loves to elevate specialists, people who drill deep into a single topic. Those people are great. But there's a place for generalists too, argues David Epstein. Jacks of all trades are often more successful than specialists. And he's got science to back it up. We talk with Epstein about his latest book, "Range: Why Generalists Triumph in a Specialized World".
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.