Hepatitis B virus is a viral infection which affects the liver and can result in permanent liver damage. It is currently the leading cause of chronic liver diseases and millions of individuals are infected with it each year. It is highly contagious and is contracted through bodily fluids. Symptoms include joint pain, fatigue, loss of appetite, vomiting, jaundice or yellowing of the skin/eyes, and fever. To prevent contracting hepatitis the Centers for Disease Control and Prevention (CDC) recommends individuals getting a hepatitis vaccine. Unfortunately, there is no cure for hepatitis B, which could lead to serious health problems.
Once an individual comes into contact with hepatitis B, the virus is transported to the liver where it replicates. The virus is then encapsulated in a protein to form a virion, which is then secreted from the cell to infect others. The precise mechanism of the hepatitis B life cycle is still unclear. Scientists are working to further understand this process and improve treatment. Interestingly, monkeys do not contract hepatitis B, so scientists are specifically investigating how this occurs to generate better therapies.
A recent study in Nature Communications, by Dr. Koichi Watashi and others, discovered how the macaque monkey immune system restricts viral entry into their liver cells. Watashi is the Director of the Division of Drug Development in the Research Center for Drug and Vaccine Development at the National Institute of Infectious Diseases in Japan. He is also a visiting professor at the Tokyo University Graduate School of Science and Technology. Watashi’s work focuses on viral infections and their mode of transportation and progression within the body.
The team used various laboratory methods, including a detailed microscopy technique called cryo-electron microscopy, to observe liver cells and the proteins on the cells’ surface. Cryo-electron microscopy is a technique to generate images of biomolecules and construct their 3D structures. Using this microscopy technique the team discovered the structure of a protein receptor on macaque liver cells. In human liver cells, hepatitis B binds to two locations that allow the infection to enter the cell. However, macaque liver cells lose these binding sites because of instability within the protein structure.
Watashi and his team compared both protein structures in humans and macaques and found that the amino acids that make up each protein differed between the species. Interestingly, humans share 96% of their amino acid sequence with macaques. However, the other 4% or 14 amino acids were distinctly different which changed protein binding sites. Consequently, macaques were resistant to hepatitis B infection. Scientists suspect this difference is due to an acquired mechanism throughout evolution that altered macaque biology to protect them from the virus.
Watashi and others discovered how macaques resist hepatitis B compared to humans. This groundbreaking development in viral biology helps uncover protein structures that allow hepatitis B to infect and replicate in liver cells. It also clearly demonstrates the evolution of other species in response to viruses throughout history. Through our understanding of species resistant viral mechanisms, scientists can better understand human susceptibility to viruses. As a result, this work provides foundational knowledge to enhance viral treatments and improve patient quality of life.
Study, Nature Communications, Koichi Watashi, National Institute of Infectious Diseases, Tokyo University