Scientists from The Pirbright Institute have used a ground-breaking approach to show how a morbillivirus that causes disease in small ruminants such as sheep and goats, known as small ruminant morbillivirus (a close relative of measles virus – the human morbillivirus), could, through minor changes in a particular protein, overcome barriers that currently prevent it from entering human cells.
Many viral pandemics start following transmission of an animal-associated virus into human populations, for example recent outbreaks of influenza virus. Diseases that jump from animals to people are known as zoonoses. Closely related viruses that affect a wide range of species are of particular concern to experts who are looking to predict the emergence of new pandemics; it is therefore important to understand and study the risks of these emergences occurring.
The successful eradication of rinderpest virus (a large ruminant morbillivirus) and the potential eradication of measles has led to concerns that small changes in other morbilliviruses, including small ruminant morbillivirus (also known as peste des petits ruminants (PPR)), could enable the disease to emerge in these so-called ‘vacated ecological niches’. Improving our understanding of what determines host-range, particularly at the genetic and structural level, will allow researchers to monitor the emergence of these viruses with increased accuracy.
In collaboration with scientists from the University of Glasgow, the University of Cambridge and other institutions, scientists from the Viral Glycoproteins Group, led by Dr Dalan Bailey, identified that a single amino acid change in the PPR virus enables it to use the human receptor SLAMF-1 to gain entry into human cells. The findings, published in the Journal of Virology, have important implications for monitoring virus evolution in the field, especially during eradication campaigns. However, equally important are the laboratory techniques used by the scientists to identify these changes. Significantly, these approaches negated the requirement for live infectious virus and high containment laboratories and meant modified live virus with potential zoonotic capability were not, and will not, be generated.
Dr Dalan Bailey who led the research explains, “By examining the zoonotic potential of non-human morbilliviruses we identified that PPRV cannot enter human cells because it does not have the correct attachment protein configuration to bind to the human SLAMF1 immune cell receptor. However, using our existing understanding of how these proteins interact, and previous sequencing and structural studies, we were able to identify and confirm that a single amino acid in the PPRV Haemagglutinin can overcome this barrier to entry.”
He added: “It is important to note that this does not mean the virus would have the potential to cause disease in humans as there are many other factors required for the virus to successfully replicate and cause clinical symptoms, but it does indicate that these viruses have zoonotic potential given the right mutations and conditions. In the light of these findings we believe it is important that a sequence surveillance programme, similar to that undertaken for influenza, is introduced to monitor mutations in this region.”
The findings presented in this study, will also inform future strategies for the development of novel vaccines. Dr Bailey is collaborating with Professors Brian Willett and Margaret Hosie at the MRC Centre for Virus Research, University of Glasgow, on a joint Department of Health and Social Care (DHSC) funded project towards the development of pan-morbilliviral vaccines. Prof. Willett commented: “If we can identify the specific features (epitopes) on the viral glycoproteins that are targeted by antibodies, we may be able to design novel vaccines that induce protective immune responses against viral zoonoses.”
Notes to editors
Peste des petits ruminants virus (PPRV) is a highly contagious virus causing an infectious disease in goats and sheep and has a death rate as high as 90%. This virus has a devastating impact on many people living in Africa, the Middle East and India who rely on livestock to survive and there have been recent outbreaks in Europe. The economic cost of the disease is estimated at US $874 million per year and despite vaccine control in areas where it is prevalent, it continues to spread into new regions.
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About The Pirbright Institute
The Pirbright Institute is a world leading centre of excellence in research and surveillance of virus diseases of farm animals and viruses that spread from animals to humans. Based in the UK and receiving strategic funding from the Biotechnology and Biological Sciences Research Council (BBSRC), the Institute works to enhance capability to contain, control and eliminate these economically and medically important diseases through highly innovative fundamental and applied bioscience.
With an annual income of nearly £32.1 million from grants and commercial activity, and a total of £14.3 million strategic investment from BBSRC during 2017-2018, the Institute contributes to global food security and health, improving quality of life for animals and people.
For more information about The Pirbright Institute see: www.pirbright.ac.uk
The Biotechnology and Biological Sciences Research Council (BBSRC) is part of UK Research and Innovation, a non-departmental public body funded by a grant-in-aid from the UK government.
BBSRC invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond.
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