Investigation of Hepatitis B Virus Capsid Function Could Lead to New Therapies

In hepatitis B, the capsid, or protein shell, encloses the virus’ genetic blueprint and drives the delivery of that blueprint to infect a host cell. Although researchers believe that the capsid is a promising therapeutic target for the infection, not much is understood about its functionality and influence on its environment.

A new study published in eLife provides insight into previously unknown details about the capsid that may have implications for the development of new drugs to treat the infection. Using computer simulations, researchers from the University of Delaware performed all-atom molecular dynamics simulations, which allowed them to study how the molecules carry out their functions.

Previous studies have used experimental microscopes to study the capsid but have not been able to provide high-resolution images of the complex structure, according to the researchers. Simulations have given researchers a better look at the capsid and how it interacts with its surroundings.

Through simulation, the researchers found asymmetry in capsid shape, revealing a highly flexible structure that suggests its ability 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,” Jodi A. Hadden, PhD, lead author of the study, said in a press release.

Knowing this detail could help lead to new drug treatments, according to the study. If the capsid could be made rigid and unable to distort, the infection process may be able to be stopped, the researchers noted.

Additionally, the researchers found that small triangular openings, or pores, in the surface of the capsid are likely where its protein “tails” poke through and send a signal that is essential to the infection process.

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

The findings indicate that disruption of the capsid could be a promising approach to the development of new therapies for hepatitis B virus.

Reference

Hadden JA, Perilla JR, Schlicksup CJ, et al. All-atom molecular dynamics of the HBV capsid reveals insights into biological function and cryo-EM resolution limits. eLife. 2018. Doi: 10.7554/eLife.32478