Virus cross-species transmission. Defining the immunological barriers to viral emergence

Lead Research Organisation: University of Glasgow
Department Name: UNLISTED

Abstract

Humans are constantly exposed to a variety of animal viruses. Understanding why most of these viruses fail to spillover and thrive in human populations is crucial to devise optimal strategies to manage viral emergence. Our programme aims to understand diverse immunological barriers to virus cross-species transmission. Our hypothesis is that the genetic and immunological variability of each individual or species helps define susceptibility or resistance to virus cross-species transmission. Our first aim is to identify those genes that are activated immediately after virus infection (known as interferon-stimulated genes, ISGs) and block respiratory viruses. Our second aim is to create a risk assessment framework to identify those specific viral proteins (and specific amino acid residues within the proteins) that favour the spillover of avian influenza viruses into the human population. The third and last aim of the programme is to understand the antibody landscape in humans and selected animal species, in order to estimate the impact of cross-neutralising antibodies and, at the population level, cross-immunity on constraining viral emergence. At the end of this programme, we will be able to translate our discoveries by delivering actionable data that can support the risk assessment of the zoonotic potential of viruses.

Technical Summary

Humans are constantly exposed to a wide array of animal viruses. Understanding why most of these viruses fail to spillover or subsequently thrive in human populations will be crucial to how we manage viral emergence. This programme aims to define and mechanistically understand diverse immunological barriers to cross-species transmission, based on the hypothesis that the genetic and immunological landscape of each individual or species helps define susceptibility or resistance to virus cross-species transmission. We have developed a comprehensive programme with three work packages (WPs), which are built upon the progress we made in the previous quinquennium (QQ). In WP1, focusing on barriers to the emergence of respiratory viruses with pandemic potential, we will use arrayed interferon-stimulated gene (ISG) expression screening (incorporating allelic and species-specific diversity) to identify antiviral ISGs that might constrain the emergence of respiratory viruses, including coronaviruses, paramyxoviruses and pneumoviruses. In WP2, we will create a risk assessment framework to identify the viral determinants that favour the spillover of avian influenza viruses into the human population and identify additional defences that specifically target animal influenza viruses. In WP3, we will focus on understanding the antibody landscape in humans and selected animal species, in order to estimate the impact of cross-neutralisation and, at the population level, cross-immunity on constraining viral emergence. Within this context, we will develop machine learning algorithms to predict human and livestock susceptibility to RNA virus infection and carry out phylogenetically informed neutralisation assays to develop predictive models of cross-protection for selected high-risk RNA viruses. This programme takes advantage of the expertise that we have accumulated at the CVR for addressing questions by comparative multispecies approaches at the human-animal interface. At the end of this programme, we will be able to translate our discoveries by delivering actionable data that can support the risk assessment of the zoonotic potential of viruses.

Publications

10 25 50

Related Projects

Project Reference Relationship Related To Start End Award Value
MC_UU_00034/1 31/03/2023 30/03/2028 £5,710,000
MC_UU_00034/2 Transfer MC_UU_00034/1 31/03/2023 30/03/2028 £3,315,000
MC_UU_00034/3 Transfer MC_UU_00034/2 31/03/2023 30/03/2028 £3,112,000
MC_UU_00034/4 Transfer MC_UU_00034/3 31/03/2023 30/03/2028 £410,000
MC_UU_00034/5 Transfer MC_UU_00034/4 31/03/2023 30/03/2028 £8,497,000
MC_UU_00034/6 Transfer MC_UU_00034/5 31/03/2023 30/03/2028 £2,987,000
MC_UU_00034/7 Transfer MC_UU_00034/6 31/03/2023 30/03/2028 £1,478,000
MC_UU_00034/8 Transfer MC_UU_00034/7 31/03/2023 30/03/2028 £2,321,000
MC_UU_00034/9 Transfer MC_UU_00034/8 31/03/2023 30/03/2028 £360,000
 
Description Blog post in Naturally Speaking 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
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Year(s) Of Engagement Activity 2024
URL https://naturallyspeaking.blog/2024/02/05/conference-presentation-prizes-what-the-judges-want-to-see...
 
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Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Chatted to Dr. Jason Goldsmith and Dr. Brenda Raud about vampire bats as a reservoir for #rabies and approaches to vaccination that could prevent transmission.
Year(s) Of Engagement Activity 2023
URL https://www.immunologypodcast.com/ep-59-infectious-disease-ecology-and-evolution-featuring-dr-daniel...
 
Description Engagement event at Glasgow Science Centre 
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 Hosted activities based around vampire bats, and how they catch and sample them in the field to test for rabies. Part of GSC's Halloween event.
Year(s) Of Engagement Activity 2023
URL https://www.glasgowsciencecentre.org/whats-on/halloween-family-party
 
Description Featured in 18 articles for research into BTN3A3 evasion 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact 18 online and physical articles. Press release published and SMC briefing held. For paper 'BTN3A3 evasion promotes the zoonotic potential of influenza A viruses' in Nature.

https://www.bbc.co.uk/news/health-66041067
https://www.reuters.com/science/scientists-isolate-human-gene-able-fend-off-most-bird-flu-viruses-2023-06-28/
https://www.thetimes.co.uk/article/scientists-find-gene-that-protects-humans-from-bird-flu-db39v3zfn
https://www.theguardian.com/science/2023/jun/28/human-gene-identified-prevents-most-bird-flu-viruses-moving-to-people
https://inews.co.uk/news/science/bird-flu-defence-discovered-genes-protect-humans-future-pandemics-2441180
https://metro.co.uk/2023/06/28/human-gene-may-protect-against-bird-flu-but-not-the-most-deadly-19028511/
https://www.nottinghampost.com/news/health/scientists-find-gene-protects-humans-8559353
https://www.aol.co.uk/scientists-identify-gene-protects-humans-150000944.html?guccounter=1
https://www.newscientist.com/article/2380281-bird-flu-viruses-have-mutations-that-might-help-them-spread-to-humans/
https://www.politico.eu/article/scientist-pinpoint-gene-protect-human-bird-avian-flu/
https://www.telegraph.co.uk/global-health/science-and-disease/bird-flu-outbreaks-antiviral-gene-scientific-research/
https://www.theguardian.com/science/2023/jun/28/human-gene-identified-prevents-most-bird-flu-viruses-moving-to-people
https://www.heraldscotland.com/news/23618961.glasgow-scientists-find-gene-stops-bird-flu-spreading/
https://www.heraldscotland.com/news/23620409.bird-flu-gene-glasgow-study-explained-five-minutes/
https://www.telegraph.co.uk/news/2023/06/28/bird-flu-human-gene-identified-stop-spread-between-people/
https://www.bristolpost.co.uk/news/health/scientists-find-gene-protects-humans-8559364
https://www.walesonline.co.uk/news/health/scientists-identify-gene-stops-humans-27218512
Year(s) Of Engagement Activity 2023
URL https://www.bbc.co.uk/news/health-66041067
 
Description Featured on BBC Scotland to speak about what to expect with COVID-19 and Flu this winter. 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Antonia Ho and Massimo Palmarini were featured on BBC Scotland to speak about what to expect with COVID-19 and Flu this winter.
Year(s) Of Engagement Activity 2023
URL https://www.bbc.co.uk/news/uk-scotland-66502574
 
Description Pablo Murcia featured on CNN Espanol 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Featured on CNN Spain to speak about Avian Flu and COVID-19. 14k views on CVR YouTube.
Year(s) Of Engagement Activity 2023
URL https://youtu.be/3GER9p5Cg50
 
Description Pablo Murcia on ITV News 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
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Year(s) Of Engagement Activity 2023
URL https://www.itv.com/news/2023-11-27/first-human-case-of-h1n2-swine-flu-detected-in-uk?utm_medium=Soc...
 
Description Radio interview on BBC Radio Scotland for BTN3A3 Research 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Radio interview. Press release published and SMC briefing held. For paper 'BTN3A3 evasion promotes the zoonotic potential of influenza A viruses' in Nature.
Year(s) Of Engagement Activity 2023
URL http://www.pressdata.co.uk/viewbroadcast.asp?a_id=29669729