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Pirbright scientists use ground-breaking techniques to identify how a ruminant virus can adapt to infect human cells

14 October 2020

Scientists from The Pirbright Institute have used a ground-breaking approach to identify that a morbillivirus that causes disease in small ruminants such as sheep and goats, known as peste des petits ruminants (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.

Diseases that jump from animals to people are known as zoonoses, and many viral pandemics start following transmission of an animal-associated virus into human populations, for example recent outbreaks of influenza virus. 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 small change to a peste des petits ruminants virus (PPRV) protein enables it to use the human receptor SLAMF-1 to gain entry into human cells.

Dr Bailey explains, “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 allow human cell entry. 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.”

An equally important element of this study was 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.

The research, published in the Journal of Virology, has important implications for monitoring virus evolution in the field, especially during eradication campaigns. “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”, offered Dr Bailey.

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 PPRV, could enable the disease to emerge in so-called ‘vacated ecological niches’. Improving 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.

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