Revealed: The surprising origins of Hepatitis A

Scientists unravel the mystery of a strange virus

Hep A Virus
Hep A Virus

Scientists have used advanced X-ray techniques at the UK’s synchrotron science facility, Diamond Light Source, to unravel the secrets of Hepatitis A: a virus that appears to be rather unique. Hep A has proved difficult to study in the past, but for the first time scientists have been able to determine the atomic structure of the virus. Their findings suggest that Hep A may be the evolutionary missing link between picornaviruses, which infect humans and animals, and some insect viruses.

Despite an effective vaccine, Hep A continues to infect 1.4 million people each year. It causes infection of the liver, and symptoms can include diarrhoea, vomiting, yellow skin, fever, and abdominal pain. Hep A is particularly hardy; unlike other viruses in the picornavirus family, which includes polio and the common cold, Hep A is able to withstand remarkably high temperatures and remain stable in hostile environments, making it difficult to control infection. It also has a unique enveloped form, whereby it shrouds itself in the host membrane, making it harder for the body’s immune system to detect.
 
But in an unprecedented step forward, a team of scientists from Beijing and Oxford have been able to determine the exact structure of Hepatitis A, down to the individual atoms. This new finding is a considerable advance for research into Hep A, and more broadly for our understanding of the virus world.
 
Having scrutinised the atomic structure of the virus, the team from the University of Oxford have concluded that Hep A possesses characteristics of both ancient insect viruses and modern human viruses such as polio. The methods by which it infects host cells, the very limited range of cells in which it thrives and the sheer stability of Hepatitis A all point towards it having somehow become stuck along the evolutionary trail. Where other picornaviruses developed into the structures we know today, Hepatitis A has remained forever frozen between the old and the new.
 
This discovery is ground-breaking for what it reveals about the history and evolution of viruses. Viruses are some of the oldest and most pervasive elements of the natural world. There are more viruses on Earth than all bacteria, plant and animal life combined, and they can evolve much faster than any living thing. Because they are so diverse and develop so quickly, it can be difficult to work out how they are related and how they evolved. Scientists know enough to group similar viruses into different families, but the question of their history and how these families came to exist in their current form has been very difficult to unravel. 
 
Hepa A virus
Hepa A virus
However, recent advances in technology have allowed scientists to look more closely at the structures of challenging viruses. Upgrades to facilities for analysing viruses at the Diamond synchrotron – which produces powerful X-ray light for scientists to use in their research – make it easier for whole viruses to be scrutinised in minute detail. Using two of Diamond’s crystallography beamlines, I03 and I24, the group have uncovered vital new insights into how viruses have evolved, suggesting how structural constraints may limit this change and confine some viruses to taking different routes to secure infection of their host.
 
Dave Stuart led the research into Hepatitis A. He points out exactly why these findings are so significant: “Viruses are too small and fragile to leave a fossil record, and change so quickly that many people would despair of piecing together the story of their evolution, so it is wonderful to see that their intricate details show mechanisms that form missing links between different families.”
 
The message is clear: the more we know about virus history and relationships, the more prepared we are to tackle viruses that pose a serious threat now and in the future; that’s why it’s so important to understand the fundamental atomic processes required for a virus to replicate and survive. This underpinning knowledge is the groundwork for the next stage, the production of improved vaccines and effective anti-viral drugs. Using advanced new technology such as Diamond, scientists are able to unpick the mysteries of even the most enigmatic viruses, atom by atom.