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Biosensor measures zoonotic potential of influenza viruses

WHEN AND HOW DOES A VIRUS ATTACH?

Biosensor measures zoonotic potential of infl uenza viruses

Better understanding of the bond between viruses and host cells contributes to predicting whether animal viruses can be transmitted to humans (and vice versa). Researchers Erhard van der Vries from Royal GD and Jurriaan Huskens and Nico Overeem from the University of Twente (Nico joined GD in November) have developed a biosensor that can measure this bond between virus and host cell. This biosensor can be used to help predict the zoonotic potential of in uenza viruses. This information is important when analysing the risk posed by zoonotic viruses, such as in uenza and coronavirus.

In uenza viruses infect a host through their receptor-binding proteins, which bind to sugar structures on the host organism’s cell surface. But how does a virus recognise human ‘host cells’, despite the cell surface being different to that seen in animals? To answer this question, researchers from Royal GD and the University of Twente replicated the surface of a cell on a micro-

Article and animation

An article on this study was published at the end of last year in the American scienti c journal ACS Central Science, under the title ‘Hierarchical multivalent effects control in uenza host speci city’. An animation was also created, to show clearly how the biosensor works and why this could have a positive impact on the protection of animal and human health.

The biosensor provides insight into how and at which density of receptors a virus binds tot different host cels.

chip, in order to understand this binding process at a molecular level. The binding process is complex: the length, structure and density of these sugars (glycans) vary between humans and animals, and a minimum number of receptor cells also appear to be required for a virus to attach to a host cell.

Important insights

The researchers created a cell surface with varying sugar densities and structures on this biosensor. This allowed the researchers to determine for the rst time the minimum sugar density needed for a virus to attach. This minimum sugar density was also highly dependent on the length and type of sugar structure. The biosensor therefore provides insight into how a virus binds to different host cells, with the minimum receptor density for avian or human-type receptors acting as a measure for the risk of zoonosis. This knowledge allows more accurate estimation of the risk of in uenza viruses being transmitted from animals to humans. These insights will also be important for future research into other zoonotic viruses, such as coronaviruses.

DECIDE

Healthier animals thanks to data

Royal GD is to undertake research together with 18 partners from 11 countries, under the leadership of Utrecht University, to establish earlier detection of endemic infectious diseases in young farm animals and salmon, so that farmers and veterinarians can take appropriate measures. This project titled ‘Data-driven control and prioritisation of non-EU-regulated contagious animal diseases’ (DECIDE) receives ten million euros of European funding.

The DECIDE project will be kicked off this summer. Project coordinator is Gerdien van Schaik. She is employed by GD and is a Professor at the Veterinary Faculty at Utrecht University, specialised in ‘Monitoring and surveillance of animal health’. “We want to help farmers to keep their animals as healthy as possible. This project focuses on young animals; calves, chicks, piglets, and on salmon in aquaculture. The major issue in young farm animals concerns endemic infectious diseases such as diarrhoea and respiratory problems. In the case of salmon, there are a number of viral infections and sea lice which cause high mortality.”

Practical tools

By gathering and applying all kinds of data on these animals, problems can be detected at an earlier stage. “An automatic drinking dispenser which registers that calves are suddenly drinking much less, for example. Or an underwater camera which shows that the salmon are eating less or are less active. That’s not something you can see from above.” The project will involve a wide range of parties, such as large pig and poultry production integrators in Spain and Italy, suppliers of automatic feedings systems for calves and underwater cameras, a Polish poultry laboratory and an international meat producer.

“The idea is that we utilise all this data to develop practical tools, which farmers and their veterinarians can use to improve animal health at their farms,” says Gerdien van Schaik. “In doing so, we pay attention to what farmers and their veterinarians

Gerdien van Schaik

Arjan Stegeman Mirjam Nielen

Wilma Steeneveld,

DECIDE project-coordinator Gerdien van Schaik with her colleagues of the Departement Population Health Sciences at Utrecht University.

actually want, as they will be using it. An app comes to mind, for example, which gives a notification when something is wrong.”

Better welfare

By means of the DECIDE project, GD hopes to improve not only animal health but also animal welfare and the agriculture/aquaculture farm economy. A number of sectors and parties can also learn from each other in the process. “Just like for salmon, you could also use cameras to monitor the behaviour of groups of chicks, for example. We hope to put such ideas into practice.” Nineteen partners from eleven European countries will collaborate in DECIDE, and nine PhD researchers will be employed in the project, two of whom at Utrecht University. The project will be initiated early this summer and will last five years.

BALANCING BETWEEN GOAL AND USED RESOURCES

Animal models for better animal health

In order to make animals healthy and keep them healthy, research sometimes needs to be carried out on these animals. To test whether a vaccine is sufficiently effective in practice or to determine whether sick animals recover after being given a new medicine. This kind of research for the benefit of animals is carried out using an animal model. The aim is always to improve the health of the farm animals that the tests are conducted on.

Royal GD has been working with animal models for many years and strives to continuously improve these. Because an animal model has to meet many requirements and regulations. Erik Engelen, who is involved in developing animal models at GD, explains: “That makes sense of course. You only carry out research on animals when there are no valid alternatives or when this is required by law. There are a lot of legal procedures that need to be followed and the animal model has to make a significant contribution to animal health.”

In the interest of animals

This last point is definitely the case. For example, GD may conduct the statutory research required to guarantee that a vaccine

Knowledge and expertise

GD has a lot of knowledge and expertise in the field of animal models, including specific expertise in the areas of animal health, data analysis and the laboratory. GD has a huge range of laboratory tests at its disposal. The company is ISO-certified and is able to carry out GLP work.

or veterinary medicine actually complies with all the necessary quality requirements. The use of good and effective vaccines in the sector prevents animal diseases, and only veterinary medicines that meet strict standards can protect animals against pathogens or help them recover. So we work together to improve animal health, in the interests of animals, their owners and society at large. Information obtained through this kind of research can sometimes also be used to promote animal health in other ways, such as to make a distinction between viruses that are harmful and less harmful, or to look which diagnostic tool is the best to make an early correct diagnosis.

Specific models

GD has an excellent international reputation when it comes to applied research, being the link between science and practical applications. “We have a lot of experience within the poultry sector in particular,” says Erik. “But of course there are other species that suffer from particular health problems too. Respiratory problems in calves or post-weaning diarrhoea in piglets come to mind for example. During the weaning period, a pig’s gastrointestinal tract undergoes huge changes. It has to go from processing easy-to-digest sow’s milk to difficult-to-digest solid food. This can cause diarrhoea and health problems. If we can check the effectiveness of veterinary medicines against these kinds of specific problems in an animal model and improve animal health, that’s obviously brilliant.”

The three Rs

You might wonder whether testing medicines on animals is responsible. In some cases there are other options, according to Erik. “For example, cells, tissues, or lower animals whose level of consciousness is (as yet) less developed, such as larvae and eggs. These kinds of alternatives are used wherever possible but, in the final stages of the development of a medicine, for example, we often do need to look at whether it does in fact also work in the target species. The three Rs always need to be taken into account when using animal models: replacement, refinement and reduction. If possible, we replace animals with other media, we refine the animal models as much as possible and we reduce the number of animals to a minimum. This last point is possible because the conditions are so strictly controlled.”

Final goal

Refinement can be achieved through innovation. “Our laboratories, facilities and equipment are becoming more advanced all the time. At the moment we’re working on biosensors. These deliver knowledge while allowing us to handle the animals less. That’s another great new development within the use of animal models.” In the end, it all comes down to improving animal health. That’s the final goal, and that goal has to be in balance with the resources used. If this is the case, you can achieve great results in the field of animal health with an animal model,” concludes Erik van Engelen.

MORE INFORMATION WWW.GDANIMALHEALTH.COM/CRO

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