Scientists at the University of St Andrews, together with colleagues from Emory University in the USA and Sun Yat-sen University in China, have uncovered the structure of a key protein from the Lassa virus which is endemic to West Africa and can cause deadly hemorrhagic fever.
The structure reveals how the virus evades its host’s immune system, and how it hijacks infected cells’ vital machinery in a process scientists call “cap-stealing”. Details of the structure could guide future efforts to develop an effective anti-viral drug and vaccine.
The findings are published in this week’s issue of Nature.
Lassa virus represents a family of viruses – arenaviruses – whose natural hosts are rodents and which cause hemorrhagic fevers in Africa and South America. New varieties of arenavirus continue to emerge, such as the deadly “Lujo” virus identified recently in Zambia and South Africa.
Lassa virus infects between 100,000 and 300,000 people every year in West Africa, with an estimated 5,000 deaths according to the Centres for Disease Control and Prevention. Most people infected experience a mild illness, but about 20 per cent suffer a severe multisystem disease with internal bleeding and immune suppression. Around one per cent of all infections are fatal. A common complication of infection is deafness.
It had been known that the nucleoprotein (NP) of Lassa virus has an essential role to play in immune suppression in sufferers but how this protein worked on a molecular level was still a mystery. However, by studying its X-ray structure the team succeeded in building an atom-by-atom 3D picture of the protein’s structure and how it operates in the body.
What they learned was that Lassa virus NP has the ability to chew up RNA, one of the viral components that usually trigger internal alarm systems within human cells. They have confirmed that it is this property that allows the Lassa virus to supress cells’ interferon production.
Dr Chang-jiang Dong, a Wellcome Trust Career Development Fellow at the University of St Andrews, said:
“Our findings are really exciting and provide great potential for vaccine and drug development. In solving the structure of the Lassa virus NP protein, we have revealed its unexpected functions and shown the unique workings of viral replication and immune evasion.
“This totally unexpected knowledge will make designing a vaccine or drug much easier. Trying to design a vaccine or drug without this kind of information is a bit like trying to make a chair-cover when the chair’s shape is a total unknown – in all likelihood it won’t fit or do its job properly. By understanding how virus proteins attack the body at the molecular level, we stand a much better chance of designing a vaccine or drug whose shape and function will successfully block the virus from developing into the acute viral illness.”
These findings also have implications for the other 22 viruses in the arenavirus family including Lymphocytic choriomeningitis virus, which has been identified as a causative agent for fatal central nervous system disease in children and fatal multi-organ failure in the elderly and organ transplant patients.
Notes to News Editors
X-ray data was collated at Diamond Light Source, the UK’s national synchrotron facility. Diamond generates extremely intense pi-point beams of synchrotron light of exceptional quality – allowing X-rays around 100 billion times brighter thatn a standard hospital X-ray machine. For more information about Diamond visit www.diamond.ac.uk
This research was supported by the Wellcome Trust and the Southeast Regional Centre of Excellence for Emerging Infections and Biodefense and the American Cancer Society.
Dr Chang-jiang Dong is available for interview on 01334 467282 or email email@example.com
Contact: Emma Shea, Communications Manager, on 01334 462 109 or email Emma.Shea@st-andrews.ac.ukResearch