The influence of dual infections on viral load and disease severity

Lead Research Organisation: University of Edinburgh
Department Name: The Roslin Institute

Abstract

Endemic and exotic virus diseases are threats to food security and, in some cases, potential zoonoses. Laboratory studies of virus pathogenesis rely on infection of “clean” animals. In nature, however, secondary infections or underlying persistent infections are likely to play a major role in determining the outcome of infection. Understanding how viruses and other pathogens interact within target species and disease transmitting vectors may lead to insights into prevention of virus transmission, infection or disease.

Publications

10 25 50
 
Description We investigated the effect of on-going herpesvirus infection on acute influenza A virus infection in a mouse model. We showed that mice latent infected with a gammaherpesvirus experienced less severe infections than naive mice. The mechanism of protection was explored using protein and QPCR arrays and showed that a primed innate immune response against the DNA virus provided for an elevated innate immune response in co-infected mice which prevented viral spread and controlled virus replication. We also investigated the effect of parasitic helminth infection on influenza respiratory disease. These experiments showed that the outcome was dependent on the stage of worm lifecycle such that co-infection either alleviated or exacerbated disease.

An ongoing study has examined the pathogenesis of Staphylococcus aureus and influenza A virus co-infection. Secondary infection of influenza-infected individuals by pathogens such as Staphylococcus aureus and Streptococcus pneumonia is a major cause of morbidity and mortality in human populations. We have identified a secreted enzyme of S. aureus that enhances influenza replication in primary cells from humans and chickens in vitro, suggesting that it may contribute to increased severity during co-infection. We are currently examining the mechanism involved in this activity.

Our epidemiological studies into bovine respiratory disease complex (BRD) have established that in Kenya, there are positive associations between infectious bovine rhinotracheitis virus (IBR), bovine parainfluenza virus Type 3 (PIV3) and bovine viral diarrhoea virus (BVDV) in East African Shorthorn Zebu calves.
Exploitation Route The coinfection studies (in the laboratory and the field) have implications for the use of live vaccines, particularly in countries where helminth infections are common, as well as for control strategies for complex disease syndromes.

We are exploring a potential application of the effect of the Staphylococcus aureus protein that enhances influenza A virus infection to enhance the yield of influenza vaccines that are propagated in chicken eggs. We established that addition of a recombinant form of the staphylococcal protein to eggs can increase the yield of influenza vaccine strains by 3-fold. This could potentially contribute to improved capacity and reduced costs for influenza vaccine production. We plan to further investigate the potential translation and commercial viability of the application.
Sectors Agriculture, Food and Drink,Healthcare

 
Description By understanding how important viral diseases interact with their hosts, we can better design intervention strategies such as novel vaccines, drugs and targeted gene drives. This may result in better farm animal production and increased human health via the reduction of the impact of animal and human diseases. BBSRC strategic investment at Roslin via this and other Institute Strategic Programmes has sustained expertise and facilities that have attracted substantial inward investment at the Easter Bush Campus. This has recently included a £15M Gates Foundation funding to establish the Centre for Tropical Livestock Genetics & Health to implement genetic gain and treatments in support of farmers in low- and middle-income farmers, including to control endemic and zoonotic diseases. It has also driven dozens of productive collaborations with industry via contracts and leveraging schemes, leading to a £10M private equity investment to form Roslin Technologies to commercialise our research and construction of a new £32M Innovation Centre adjacent to the Institute to engage and grow businesses. Moreover, the expertise supported by this funding has attracted major investment in Agri-Tech Centres at Easter Bush funded by InnovateUK (Centre for Innovation Excellence in Livestock & Agri-EPI). These Centres will increase national capacity for infectious challenge in farmed animals, gene editing and collection of novel phenotypes and be linked to stakeholders throughout the food supply chain.
First Year Of Impact 2013
Sector Agriculture, Food and Drink,Education,Healthcare
Impact Types Economic

 
Description Expert group member on coronavirus for for DISCONTOOLS
Geographic Reach Europe 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
Impact The policy is currently in work.
 
Description CALL: INTEGRATING AND OPENING RESEARCH INFRASTRUCTURES OF EUROPEAN INTEREST
Amount € 10,000,000 (EUR)
Funding ID H2020-INFRAIA-2016-1 project number 731014 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 04/2017 
End 03/2022
 
Description Mobility grant for staff teaching/training
Amount £804 (GBP)
Organisation erasmus + 
Sector Public
Country United Kingdom
Start 12/2016 
End 03/2017
 
Description ZEIDA
Amount £25,000 (GBP)
Organisation Zoetis 
Sector Private
Country United States
Start 04/2015 
End 04/2017
 
Title CDCD pig model 
Description We improved a caesarean-derived, colostrum deprived pig model to ensure that animal welfare and survivability of pigs increases. 
Type Of Material Improvements to research infrastructure 
Year Produced 2014 
Provided To Others? No  
Impact Survivability of pigs increased from 50% to 90-100% 
 
Description Annual Roslin Institute Open Doors Day 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact The annual Roslin Institute Open Doors day was held on 14 October 2017 and was attended by 491 people. It involved 81 members of staff and students and showcased a wide range of research arising from BBSRC strategic investment, including (but not limited to), food safety, influenza, genetic improvement, DNA, imaging and the ethical treatment of animals in research.
Year(s) Of Engagement Activity 2017
 
Description Edinburgh Science Festival, Flu Fighters 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Participated in Flu Fighters during the Edinburgh Science Festival 2015.
We showcased the exhibit 'Flu Fighters' at the festival. The 'Flu Fighters' exhibit focuses on influenza viruses and the science behind the varied approaches to combating flu being developed at Roslin and Pirbright. It showcases current research including GM animals, novel approaches to vaccines and diagnostic tests and host/virus genetics.
The exhibit also demonstrates how flu transmits from animals to humans and highlight the challenges of preventing large-scale outbreaks.The 'Flu Fighters' exhibit provides an opportunity for visitors to run diagnostic tests on a chicken, design their own flu virus and discuss the pros and cons of genetic modification of animals.
Over 100 people attended the morning and the activities sparked questions from both children and parents/carers. A better understanding of the problem for the poultry industry, eco system (wild birds) and human health was reported back.
Year(s) Of Engagement Activity 2015
 
Description Flu Fighters public exhibition stand 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact 4. With £10k BBSRC funding, ISPG4-funded researchers jointly developed 'Flu-Fighters', an interactive exhibit suitable for children and adults highlighting our research to create influenza-resistant farm animals, develop improved vaccines and diagnostic tests, and understand the role of viral and host factors in the outcome of infection. This was run over three days in November 2014 at the Great British Bioscience Festival (visited by over 6500 people) as part of BBSRC's 20th anniversary programme. ISPG4 scientists were involved in running it again at the Royal Society's 2015 Summer Science Exhibition in London.
Year(s) Of Engagement Activity 2014,2015,2016
 
Description Invited talk European Veterinary Vaccinology Workshop 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Talk on career opportunities in academia for young scientists
Year(s) Of Engagement Activity 2018
URL https://www.youtube.com/watch?v=hTujbImUCcI
 
Description Membership of a guidance committee on PCV2 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Expert Group on PCV2 for DISCONTOOLS FP 7 project, funded by DG Research
Year(s) Of Engagement Activity 2006,2008,2009,2011,2013,2015,2017,2019
 
Description Mercks Digital Journal 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Online publication: De Castro AMMG, Opriessnig T. PCV2 genotypes and cross protection. Mercks digital magazine. 2019
Year(s) Of Engagement Activity 2019
 
Description Swine Practitioner workship - Vietnam 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 150 practitioners attended a workshop to learn about new strategies on virus control in pigs.
Year(s) Of Engagement Activity 2018
 
Description Swine Practitioner workshop 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Practitioner meeting in France to inform them on new insights on vaccination protocols.
Year(s) Of Engagement Activity 2017
 
Description Swine Practitioner workshop - Brazil 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 200 pig vets attended a workshop on updates on current pig diseases.
Year(s) Of Engagement Activity 2018
 
Description Swine Practitioner workshop - France 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Practitioners discussed the pro and cons of control of swine diseases in France.
Year(s) Of Engagement Activity 2019
 
Description Swine Practitioner workshop - France 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Key opinion leaders from Asia were invited to discuss advances in PCV2 research including control and diagnostics.
Year(s) Of Engagement Activity 2018
 
Description Swine Practitioner workshop - Germany 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact 3--40 veterinarians/industry representatives discussed other approached to diagnose and treat infectious disease in pigs.
Year(s) Of Engagement Activity 2019
 
Description Swine Practitioner workshop - Italy 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact 50-60 practitioners discussed other approached to diagnose and treat infectious disease in pigs.
Year(s) Of Engagement Activity 2019
 
Description Swine Practitioner workshop - Korea 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact We discussed novel approaches to diagnose and treat infectious disease in pigs. We also discussed to make a workshop in China which will occur in November 2020
Year(s) Of Engagement Activity 2019