The emergence of Zika virus in Brazil: investigating viral features and host responses to design preventive strategies.

Lead Research Organisation: University of Glasgow
Department Name: MRC Centre for Virus Research

Abstract

Zika virus is an arbovirus that belongs to the Flaviviridae family and was initially isolated from rhesus monkeys in Uganda in 1947. The most common reported symptoms are rash, fever, arthralgia, and conjunctivitis. The majority of the patients experiences only a mild and transitory disease, but severe neurologic complications have been described. The virus, previously described in Africa and oher parts of the world, has recently emerged in Brazil. It is thus a good example of how viruses can emerge around the world and start transmission cycles in novel environments. Zika virus is predominantly transmitted by Aedes species mosquitoes such as Ae. aegypti. Brazil is a large (8.5 million km2), predominantly tropical area. There are five geographical regions (North, Northeast, Center-West, Southeast and South) and five climate zones: Equatorial, Temperate, Central Brazil Tropical, Eastern Northeast Tropical and Equatorial Zone Tropical. Such characteristics favor the proliferation of Ae. aegypti mosquitoes that are dispersed around all the 27 Brazilian Federative Units in more than 3,587 cities. Besides dengue viruses, other arboviruses are now circulating in Brazil. In 2014, a total of 41 chikungunya importations and 27 autochthonous cases were detected in northeast Brazil. More recently, 34 cases of ZIKV infection have been confirmed by the Brazilian Ministry of Health. The confirmed cases occurred in eight of the 27 Brazilian states and are distributed in the Northeast, North and Southeast regions of the country, suggesting that the infection is widespread. The source of these outbreaks and the potential for virus establishment in Brazil is still not known. Arboviruses such as Zika have the potential to initiate large scale epidemics, and these infections can be extremely debilitating in absence of any specific treatments or vaccine. Thus, this newly emerged arbovirus represents a serious social and economic threat, especially because of the excessive demand on health services by the poor population. Zika virus symptoms are related to already circulating human arboviruses such as dengue and chikungunya. Thus diagnosis of Zika virus infection on the basis of clinical syndromes is not reliable and needs to be confirmed by laboratory diagnosis. Indeed, misinterpretation may have consequences for treatment but also the general understanding of pathogens local populations are at risk from. Current Zika virus diagnosis is based on molecular techniques only accessible to a few highly specialized laboratories. This project proposes to better understand the spread and epidemiology of Zika virus infection by understanding individual cases and analyse full virus genomes to put them into a global context. It will also aim to develop more easily accessible diagnostic tools that can be used in wider settings thus supporting the local health systems. At this point, it is also crucial to investigate the underlying biological processes involved in Zika virus pathogenesis and how the virus interacts with host responses, which could lead towards more effective treatment of confirmed cases. Moreover this project aims to develop tools to understand and manipulate the viral genome (called "reverse genetics") with view of better understanding viral genes, replication etc. These tools can also form the backbone of future vaccines. The strength of this project is the coming together of experts from different research areas to study the questions outlined above with the aim of significantly improving our understanding of Zika virus biology, impact on public health and study this emerging virus. This is highly relevant to Brazil, but also other regions and countries affected by this virus.

Technical Summary

The mosquito-borne flavivirus Zika has recently emerged in Brazil, where large potential vector populations (Aedes aegypti mosquitoes) exist. This virus had been detected in Africa and other tropical regions of the world, but was imported into Brazil in all likelihood in the recent past. Symptoms can be similar to dengue virus or the also recently emerged chikungunya virus, thus complicating diagnosis, treatment and intervention strategies. Indeed, very little is known about the biology and molecular biology of Zika virus, but diagnosis currently also requires specialist set ups. Thus, the potential impact of this pathogen needs to be assessed and public health preparedness improved. This project brings together experts from various fields to work on the following aims that impact on our understanding of Zika virus: (i) monitor Zika virus circulation in selected areas (including virus isolation and genetic characterisation) and develop improved diagnostic methods to identify Zika virus; (ii) use patient material for immunological studies on Zika virus infection (cytokines and antibody responses, gene expression) and set up a mouse model to assess intervention strategies and study pathogenesis further; (iii) develop an infectious clone of Zika virus for reverse genetics studies of the virus and vaccine design (including tools to produce virus-like particles); (iv) study viral antagonism of host responses at cellular level. As arbovirus infections are on the rise, there is an urgent need to share knowledge and improve the capacity response of research centers. Effective collaborative projects and networks can lead to effective ways to disease control, and this network on Zika virus can in the long term also help other countries affected by this virus.

Planned Impact

Zika virus is a newly emerged flavivirus in Brazil which is transmitted by aedine mosquitoes. Given the geography and socio-economics of Brazil, the risks associated with this novel human pathogenic may be considerable. This adds to the presence of human pathogenic mosquito-borne viruses which already have considerable public health impact; in particular dengue virus or the recently emerged chikungunya virus which can present similar disease symptoms and thus complicate diagnosis, treatment and preventive efforts. With regards to Zika virus, recent studies have focused on monitoring the virus and data about the current impact in Brazil have now confirmed its presence in parts of Brazil. It may spread further as vector mosquitoes are widely distributed across the Brazilian territory. It is important to develop measures to distinguish Zika infections from other circulating arboviruses and obtain correct public health data. There is still a lack of reliable methods for the early and accurate diagnosis of Zika virus infection. Currently Zika virus diagnosis is based on virus genome detection by either PCR or quantitative Real Time PCR (qRT-PCR); however, these methodologies demand specialized laboratories and well trained people which leaves only a few laboratories in Brazil able to diagnose this infection. At the host level, Zika virus immunopathogenesis is a largely unknown process as there are no data about cytokine and chemokine responses that are participating in host responses, and how the immune system contributes to the disease process. Based on this, a better understanding of virus biology can provide new therapeutic targets and more efficient ways to control the disease spreading in Brazil and other countries. Moreover we aim to develop a reverse genetics system and virus-host interaction studies that will allow better understanding and manipulation of the virus with the aim to vaccine development.
This consortium brings together experts from Fiocruz and the MRC-University of Glasgow Centre for Virus Research. Both partners include scientific groups with considerable expertise in key areas of the project. As consequence, the Fiocruz - MRC-University of Glasgow Centre for Virus Research integration will further enable Zika virus investigations by a team of multidisciplinary researchers and active exchanges of research that will enhance the capacity of the partner in Brazil to deal with this infection and thus enhance the local capabilities to deal with Zika virus and set up an efficient research programme. Indeed, the integration of scientific groups with expertise in molecular virology, immunology, genetics and vaccine development as brought together in this project will lead to strong interactions and a consortium capable of (i) improving viral diagnostics in a manner that is supportive of public health efforts in Brazil, (ii) understand ZIKV outbreaks in Brazil, (iii) contribute to future measures in treatment and prevention of ZIKV infections, and (iv) enhance the research capabilities and scientific impact of the Brazilian research partner, Fiocruz. The exchange of skills and expertise at the heart of our proposal, makes this a dynamic and timely combination of projects, which is likely to be relevant beyond the duration of this interaction. This collaboration will set the pace for future projects in this area. Our results will impact on policy (prevention, treatment, diagnostics) as well as point towards preventive measures.

Publications

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Gatherer D (2016) Zika virus: a previously slow pandemic spreads rapidly through the Americas. in The Journal of general virology

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Royle J (2017) Differential effects of lipid biosynthesis inhibitors on Zika and Semliki Forest viruses. in Veterinary journal (London, England : 1997)

 
Description House Commons, Science and Technology Committee Witness
Geographic Reach Multiple continents/international 
Policy Influence Type Gave evidence to a government review
 
Description Support of Fiocruz Recife Arbovirus Reference Laboratory
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
 
Description pre-SAGE UK Government Advisory Group: Zika virus outbreak
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description Horizon 2020 Zikalliance
Amount € 11,964,209 (EUR)
Funding ID 734548 
Organisation European Union 
Sector Public
Country European Union (EU)
Start 10/2016 
End 09/2020
 
Description Liverpool School of Tropical Medicine -Confidence in Concept "Hypersialylated blockers of Zika virus (ZIKV) infectivity and neuropathology" (led by R. Pleass)
Amount £47,789 (GBP)
Organisation Liverpool School of Tropical Medicine 
Sector Academic/University
Country United Kingdom
Start 02/2019 
End 10/2019
 
Description MRC Wellcome Trust Zika Rapid Response "Zika: Association studies with Guillain- Barré syndome and neurotropism" (led by H. Willison)
Amount £0 (GBP)
Funding ID MC_PC_15105 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 03/2016 
End 09/2017
 
Description MRC Wellcome Trust Zika Rapid Response "Zika: The ecology of Zika transmission in Colombia and Ecuador" (led by H. Ferguson)
Amount £0 (GBP)
Funding ID MC_PC_15081 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 03/2016 
End 09/2017
 
Description Arthropod innate immune control of arbovirus replication 
Organisation Bernhard Nocht Institute for Tropical Medicine
Country Germany 
Sector Hospitals 
PI Contribution Arbovirus clones/infectious clones, assay systems, reagents; experimental design and and data interpretation.
Collaborator Contribution Arbovirus clones/infectious clones, assay systems, reagents; experimental design and data interpretation. With Professor Esther Schnettler.
Impact Novel data on arthropod antiviral immunity to arbovirus infection; publications listed with the relevant awards.
Start Year 2015
 
Description Arthropod innate immune control of arbovirus replication: novel cell systems 
Organisation University of Surrey
Country United Kingdom 
Sector Academic/University 
PI Contribution Testing and characterisation of genetically modified mosquito cell clones.
Collaborator Contribution Production of genetically modified mosquito cell clones. With Dr Kevin Maringer.
Impact New genetically modified cell lines with defined knockouts resulting in deficiencies in RNA interference pathways.
Start Year 2016
 
Description Eco-epidemiological surveillance of Zika virus in Colombia and Ecuador 
Organisation University of Glasgow
Department Institute of Biodiversity, Animal Health and Comparative Medicine
Country United Kingdom 
Sector Multiple 
PI Contribution Deep sequencing of RNA from collected mosquitoes and data analysis for virus detection in mosquitoes; supervision of PhD student and Master's student.
Collaborator Contribution Organisation of trapping/collections of mosquitoes; supervision of PhD student and Master's student. With Dr Heather Ferguson, University of Glasgow; funded through her MRC-Wellcome Trust Zika Rapid Response funding.
Impact Data on presence of arboviruses and mosquito-only viruses in areas of Ecuador and Colombia; training of students in molecular techniques.
Start Year 2016
 
Description Hypersialylated blockers of Zika virus (ZIKV) infectivity and neuropathology 
Organisation Liverpool School of Tropical Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Arboviruses and reagents.
Collaborator Contribution Antibody fragments to be assessed for antiviral activities ( receptor binding, virus-binding etc.). Led by R. Pleass (LSTM). Neural culture systems. Led by C. Linington, H. Willison, J. Edgar, S. Barnett (University of Glasgow).
Impact Collaboration funded by Confidence in Concept grant "Hypersialylated blockers of Zika virus (ZIKV) infectivity and neuropathology" by Liverpool School of Tropical Medicine, as outlined in the relevant section.
Start Year 2019
 
Description Hypersialylated blockers of Zika virus (ZIKV) infectivity and neuropathology 
Organisation University of Glasgow
Department Institute of Infection, Immunity and Inflammation
Country United Kingdom 
Sector Academic/University 
PI Contribution Arboviruses and reagents.
Collaborator Contribution Antibody fragments to be assessed for antiviral activities ( receptor binding, virus-binding etc.). Led by R. Pleass (LSTM). Neural culture systems. Led by C. Linington, H. Willison, J. Edgar, S. Barnett (University of Glasgow).
Impact Collaboration funded by Confidence in Concept grant "Hypersialylated blockers of Zika virus (ZIKV) infectivity and neuropathology" by Liverpool School of Tropical Medicine, as outlined in the relevant section.
Start Year 2019
 
Description Infectious clones of Zika virus 
Organisation University of Tartu
Department Institute of Technology
PI Contribution Design and testing of recombinant Zika virus (produced from infectious clones obtained from the collaborator) in arthropod systems (cells, live organisms).
Collaborator Contribution Design and cloning of Zika virus for reverse genetics purposes.
Impact Publications with Professor A. Merits using Zika virus infectious clones. Listed below: https://www.ncbi.nlm.nih.gov/pubmed/29102599 https://www.ncbi.nlm.nih.gov/pubmed/29040304
Start Year 2016
 
Description MRC-Confap Newton Fund 
Organisation Oswaldo Cruz Foundation (Fiocruz)
Department Fiocruz Pernambuco
Country Brazil 
Sector Hospitals 
PI Contribution This is the collaboration on Zika virus supported by the award "The emergence of Zika virus in Brazil: investigating viral features and host responses to design preventive strategies". It is noted here for completeness as this award was a collaborative partnership. Key work areas at CVR were the development of tools to study Zika virus and virus host interactions.
Collaborator Contribution Provision of virus strains and other material; development of diagnostic tools and patient cohorts for further study. Collaborators at Fiocruz, Recife (Brazil; ODA recipient country) were Drs Lindomar J. Pena and Rafael Freitas de Oliveira Franca.
Impact The following text lists keys outcomes and points relating to ODA compliance, as also indicated in the section "Other Outputs & Knowledge/Future Steps". This collaborative project was carried out with colleagues Lindomar J. Pena and Rafael Freitas de Oliveira Franca at Fiocruz, Recife, Brazil as key collaborators. This city in the north of Brazil, an ODA recipient country, was affected by Zika virus (including cases of microcephaly). The research carried out in the context of this award was important to increase basic understanding of Zika virus at the start of the outbreak (and eventually beyond), thus playing an important role in the early work on this virus which had a major impact on public health in Brazil, and also other countries across the Americas. Key findings of the project include full sequence information of Zika virus isolated in Recife, Brazil and analysis of viral host reponse antagonism (by sfRNA and viral proteins). The project also involved other researchers at CVR and beyond, leading to collaborations on various aspects of Zika virus-host interactions and preventive measures (such as vaccine development) which will hopefully in time have a direct impact on affected countries such as Brazil. With permission from Fiocruz Recife (MTA) the isolate of Zika virus was distributed by CVR to over 25 laboratories across Europe and other parts of the world, to carry out research on this virus thus the project indirectly supported research by others with a relevant strain of this virus, which may support efforts in understanding pathogenesis and prevention. Both Drs Freitas de Oliveira Franca and Pena fully participated in the research and publication process where appropriate. They were promoted from Assistant to Adjunct Researchers, and according to information from Dr Freitas de Oliveira Franca participation in an international project helps career progression. Dr Freitas de Oliveira Franca also became involved in the setting up of the Fiocruz Arbovirus Reference Laboratory, which since November 2015 played a critical role in Zika virus diagnostics (and work in this area was further supported by this award); this structure is officially recognised by the Brazilian Ministry of Health to support the diagnosis of arboviruses and supports technical training of professionals from public laboratories (public health system) to transfer and implement molecular diagnosis of arboviruses in secondary public laboratories as well as performing non routine tests and investigation of complex cases. By doing so the Fiocruz Arbovirus Reference Laboratory contributes to the National Guide of Arbovirus Diagnosis, which is a national protocol used to provide the correct laboratorial protocols and practices to the diagnosis of dengue, Zika and chikungunya viruses. Funding by Fundação de Amparo à Ciência e Tecnologia de Pernambuco (APQ-0044-2.11/16, the Brazilian counterpart funding this UK-Brazil collaborative project) was important to implement tools for Zika virus investigations, including PCR protocols and virus isolation that were further used as positive control for PCR reactions and as antigen for in-house produced ELISAs. The project also supported the acquisition of laboratory supplies and minor equipment necessary for Zika virus investigations. Funding was subsequently acknowledged in three publications by our collaborators at Fiocruz Recife: https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-018-3313-4 https://pubs.acs.org/doi/10.1021/acsomega.7b00608 https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0005583 These are important subsequent impacts of this project-research data, likely impact on career progression and support with developing diagnostics and tools- that arose from this project and benefit our collaborators and Brazil. The Arbovirus Reference Laboratory is now involved in further studies for example ZikaBra, a project currently supported by WHO and Brazilian Ministry of Health and aiming to investigate the persistence of Zika virus in different body fluids. The project is overall supporting aims towards UN Sustainable Development Goal 3 (Good Health and Well-Being).
Start Year 2016
 
Description Proteomic investigations of Zika virus infection 
Organisation University of Glasgow
Department Polyomics Facility
Country United Kingdom 
Sector Academic/University 
PI Contribution Experimental design and data analysis; reagents; laboratory space and support for Professor Carolina Ramírez Santana (visiting Professor, Universidad de Nuestra Señora del Rosario, Colombia).
Collaborator Contribution Experimental design and data analysis; reagents for proteomics; laboratory space, support and Newton Fund support for hosting Professor C. Ramírez Santana (visiting Professor, Universidad de Nuestra Señora del Rosario, Colombia). Lead collaborator at the University of Glasgow is Dr R. Burchmore.
Impact Interaction data of cellular proteins with Zika virus E protein; one E-interacting partner is being further investigated for functional and mechanistic relevance.
Start Year 2017
 
Description Recombination in Zika virus 
Organisation University of St Andrews
Country United Kingdom 
Sector Academic/University 
PI Contribution Zika virus reagents and assays; experimental design. Hosting of PhD student from the University of St. Andrews and provision of training.
Collaborator Contribution Viral recombination assays; the project is led by Professor D. Evans and involves one PhD student.
Impact Training of PhD student at CVR in techniques for working with Zika virus.
Start Year 2016
 
Description Salmonella-Zika vaccine platform 
Organisation Newcastle University
Country United Kingdom 
Sector Academic/University 
PI Contribution Experimental design; provision of reagents.
Collaborator Contribution Production of recombinant Salmonella to express Zika virus structural proteins as vaccine candidate. With Dr Anjam Khan.
Impact Expression system for Zika virus E protein produced. Vaccination studies with the Samonella system were not successful.
Start Year 2016
 
Description Zika virus detection by the vertebrate innate immune system 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution Provided biological material such as RNA from infected cells to collaborators (Prof. Jan Rehwinkel, University of Oxford); involved in experimental design and data analysis.
Collaborator Contribution Assays for innate immune pathway activation/viral RNA detection and inhibition of signalling pathways by Zika virus proteins.
Impact Improved understanding of Zika virus innate immune detection by the human innate immune system, and viral antagonism thereof. This is important to understand the pathogenesis of Zika infection. This interaction resulted directly two publications: https://www.ncbi.nlm.nih.gov/pubmed/29572905 https://www.ncbi.nlm.nih.gov/pubmed/27706161
Start Year 2016
 
Description Zika virus sfRNA and impact on the cellular transriptome 
Organisation University of Glasgow
Department MRC - University of Glasgow Centre for Virus Research
Country United Kingdom 
Sector Academic/University 
PI Contribution Experiments with Zika virus sfRNA in immune pathway deficient cell lines; transcriptomics and data analysis carried out by CVR sequencing service and bionformatic support, respectively.
Collaborator Contribution Provision of various immune pathway deficient cell lines; testing of sfRNA impact on immune signalling (control experiments). With Professor John McLauchlan (CVR).
Impact Cell line transcriptomes in presence or absence of Zika virus sfRNA; these data are being further analysed.
Start Year 2017
 
Description Zika virus vaccine design and antibody production 
Organisation University of Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution Provision of Zika virus and derived material; experimental design.
Collaborator Contribution Development of expression systems for Zika virus structural proteins; immunisation and antibody development/neutralisation assays. With Professor Arvind Patel, Centre for Virus Research. Also includes a jointly supervised PhD student on this topic since 2017.
Impact Antibodies and neutralisation assays for Zika virus; vaccine candidates. One paper published: https://www.ncbi.nlm.nih.gov/pubmed/29934593
Start Year 2016
 
Description Zika-virus host interactions: evolution and persistence 
Organisation École normale supérieure de Lyon (ENS Lyon)
Country France 
Sector Academic/University 
PI Contribution Exchange of reagents and data that relate to Zika virus evolution; data evaluation; experimental design.
Collaborator Contribution Testing of specific aspects of Zika virus evolution under pressure of the immune system.
Impact Non yet.
Start Year 2016
 
Description Zika: association studies with Guillain- Barré syndome and neurotropism 
Organisation University of Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution Zika viruses and virology expertise; experimental design and experiments involving infections; data evaluation and interpretation.
Collaborator Contribution Murine CNS and PNS cultures; neurobiology reagents; experimental design; data evaluation. With Professor Hugh Willison, Professor Sue Barnett, Professor Chris Linington and Dr Julia Edgar through their ZIKAPlan and MRC-Wellcome Trust Zika Rapid Response funding.
Impact Improved understanding of Zika virus neurotropism and robust cell culture based Zika virus infection system for CNS/PNS studies. One paper currently published: https://www.ncbi.nlm.nih.gov/pubmed/28645311
Start Year 2016
 
Description April 2018 - NCCPE Academy - Claire Donald 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact In April 2018 CVR postdoc Claire Donald applied for the NCCPE Academy for public engagement. This incentive was supported by funding from the MVLS to support travel and accommodation to allow Claire to attend a series of workshops intended to provide bespoke development for early career researchers with an interest in public engagement and possibly a future career in the field.
Year(s) Of Engagement Activity 2018
URL https://www.publicengagement.ac.uk/
 
Description August 2017 - World Mosquito Day Blog post series 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact In August 2017 we published one blog post a day over the course of a week to provide information about the research of 7 CVR researchers involved in mosquito-borne disease research. Each researcher was asked to provide copy and images for each post. Over the course of 7 days, we received 524 views/reads of our blog, demonstrating that a series of posts appeals and entices repeat following and engagement. Each blog post was shared on social media with an average minimum reach of 500 per post - http://cvr.academicblogs.co.uk/2017/08/
Year(s) Of Engagement Activity 2017
URL https://www.facebook.com/centreforvirusresearch/
 
Description BBC reporter Ken MacDonald special report - October 2018 
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 Media (as a channel to the public)
Results and Impact In October 2018 the MRC press office arranged a visit and interview with BBC reporter Ken MacDonald. Alain Kohl, Claire Donald, Ben Brennan and Emilie Pondeville have been interviewed for a special feature about the mosquitoes and ticks that play a vital role in their research here in Glasgow. the story received coverage on BBC radio Scotland and aired on BBC Scotland television on 31 October - https://www.bbc.co.uk/news/uk-scotland-46032486?fbclid=IwAR3c0mhoBS1EA3XF5pxcDtO9pQOl4VYvCaJz85MYUeMDCEvqh2swzP-Y9ZI

This was an important opportunity to allow the CVR to share information about our centre out with a virus outbreak.
Year(s) Of Engagement Activity 2018
URL https://www.facebook.com/centreforvirusresearch/
 
Description Brownie, Guide, Scout and Rainbow Workshops - Nov 2017 - present (2019) 
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 CVR postdoc Claire Donald, Sara Elg (former CVR Research Technician) and CVR Store Manager Michelle Pearson have all had a pre-existing and long-standing relationships, supporting local guide groups in their spare time. Claire was approached by one of the Guide groups in the Fife area and was asked to run an evening of science activities for the group.

The following is an evaluation report created by Claire Donald following the initial event:

'Exhibition Details:
The initial night at the 1st Cairneyhill Guides consisted of 4 outreach activities. The girls were split into groups of 4/5 and rotated around each activity spending approximately 10mins at each one. The activities included 'Build a Virus' (with Zika, HCV and Ebola model options), origami viruses, jelly cells and pages from the CVR colouring book. There was adequate space for each of the activities and knowing the exact number of people attending allowed us to be fully prepared with ample materials, the number of volunteers who went along as well as being able to anticipate what level we needed to pitch at. Both volunteers were experienced and able to handle the questions posed. Overall the event was a very positive experience for our researchers and got a good response from the girls involved.

Stand visitors:
The evening was held at the Guide meeting place (Cairneyhill Scout Hall) and was organised into 4 stands. The maned activities were Build a Virus and the jelly cells while the origami viruses and colouring sheets were supervised by the Guiders. After 10mins at the activity, the groups rotated so everyone got a chance to try each activity. The girls were between 10-14 years old although most were around 11-12. The guide unit posted pictures on their Facebook page whilst we were there and the CVR tweeted after the event.

Feedback:
We used a sticker ratings chart in order to assess the impact of participation as a positive learning experience for all the Guides involved. We received positive feedback throughout the session but we were also able to glean interesting insights into their perception of viruses and infection. Having set numbers at each table for a set time allowed us to control what we said so that everyone at the table could get as much from the experience as possible.

All of the activities were well received as evidenced by the feedback sticker sheet we gave the girls. The girls were very engaged with the researchers and asked excellent questions. Many already had a bit of science background from parents etc and were keen to get involved in all the activities. We passed our contact details onto the Guiders in charge and allowed them to pass them on to other interested units. We had a response the next day from another guide unit keen to have us along!'

Project development
Following the success of this initial event, further requests for sessions with different groups began to be directed to Claire and Michelle from across the wider Glasgow area and Fife. As word continued to spread, this began to extend to Scout groups and then to Rainbows. In total, CVR researchers volunteered to run a total of 22 workshops varying in size range from 1 February - 29 November 2018. We estimate that we have reached an audience of approximately just over 550 young people between the 4 - 18 age range, plus a minimum of 42 youth group leaders aged >18.

In total 6 CVR researchers, 4 UofG undergraduate students and a member of UofG library staff were involved in running the 22 sessions.

Learnings/activity development
Following an initial session with a Rainbow group, it became apparent that more suitable activities were required to hold the attention of this younger age group. This offered a development opportunity for Claire and Michelle who went on to devise and develop two new activities - one involving making handmade soap to encourage discussion around the spread of viruses and one involving UV glow powder and torches, again to promote discussion around hand hygiene. Both activities proved to be incredibly popular with the younger age groups but were found to be equally useful for slightly older children.

As the number of activities continued to increase, the programme of confirmed events was shared with the UofG public engagement forum to ask for support and involvement across the wider university. This led to a member of staff from the university library becoming involved in supporting the sessions.

Evaluation summary
A mix of methods were used to evaluate the sessions. Simple sticker charts and post it notes were used to collect thoughts from the youth groups. CVR researchers also asked question about their interest in science both at the start and end of sessions verbally. Verbal feedback was also obtained from the group leaders. We also monitored social media activity by the group leaders and given the number of requests for a high number of sessions, we took this as very positive feedback taking what was initially a single workshop to a total of 22 events.

Follow-up activity
Longer term, CVR researchers intend to continue the sustainability of this project by making teaching resources for activities available on the CVR Public Engagement webpages as well as running a session for group leaders in 2019 to provide education on running sessions for future groups.
Year(s) Of Engagement Activity 2017,2018
URL https://www.facebook.com/centreforvirusresearch/
 
Description Claire Donald - I'm a Scientist June 2019 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact Postdoc Claire Donald applied and was accepted to participate in the MRC I'm a Scientist competition as part of the MRC Festival 2018. Claire formed part of a panel of scientists who would spend 1 hour per day logged into an online forum where they would answer questions from school pupils from schools across the UK. Ultimately, pupils were asked to vote for an overall winner based on the scientist they believed had provided the best responses.
Year(s) Of Engagement Activity 2018
URL https://www.facebook.com/centreforvirusresearch/
 
Description Claire Donald - Pint of Science - 26 April 2018 
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 Claire Donald (postdoc) delivered a talk about Zika virus at the 2018 Pint of Science Event in Glasgow. The theme of the evening was 'From viruses to deadly fungi and 'Novel ways to control parasites from poo',
Year(s) Of Engagement Activity 2018
URL https://www.facebook.com/centreforvirusresearch
 
Description December 2017 - CVR Public Engagement Awards 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact In December 2017 we presented 10 researchers involved in public engagement activity across the centre to recognise their efforts during the Christmas staff meeting as part of our commitment to reward and recognition. Recipients offered very positive feedback and were delighted to have their efforts recognised in front of their peers.
Year(s) Of Engagement Activity 2016,2017
URL https://www.facebook.com/centreforvirusresearch
 
Description December 2017 - Stephanie Cumberworth Interview 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Undergraduate students
Results and Impact In December 2017 CVR PhD student Stephanie Cumberworth was interviewed and filmed for a short clip to help share her research and experience of doing a PHD at the CVR. The clip was shared on the CVR Facebook and Twitter page and used as an opportunity to promote the CVR PhD programme 2018. Stephanie found the experience positive from a development point of view and the film has been viewed 68 times on youtube.
Year(s) Of Engagement Activity 2017
URL https://www.facebook.com/centreforvirusresearch/
 
Description First International Workshop on Zika Virus, Oswaldo Cruz Foundation FIOCRUZ, Northeast Brazil March 2016 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact This workshop brought together scientists and clinicians at the start of the Zika virus outbreak in Recife, Brazil. The event also included the participants in this collaboration between MRC-University of Glasgow Centre for Virus Research and Fiocruz Recife, Brazil (Drs Alain Kohl, Lindomar J. Pena and Rafael Freitas de Oliveira Franca). It covered topics from arboviruses/Zika/vaccines, virus-vector interactions, clinical aspects to diagnostics that were relevant to the outbreak. While primarily aimed at an academic audience, presence of media and politicians was noted. Over 600 participants and live web streaming received over 4000 accessions from 26 countries indicate relevance, success and reach of this event.
Year(s) Of Engagement Activity 2016
URL https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0004760
 
Description Garscube Rodeo 16 April 2018 
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 CVR Attendees:

Claire Donald (Research Associate)
Sara Elg (Research Technician)
Michelle Pearson (CVR Stores Manager)
Margus Varjak (Research Associate)
Betty Lau (Research Assistant)
Emma Duncan (UofG Undergraduate)
Hannah (UofG Undergraduate)

Exhibition Details:

The CVR arranged for a stand at the 2018 rodeo and brought along our 'Build a Virus' (with Zika, HCV and Ebola model options) activity. There was a steady stream of people throughout the day, most of whom seemed to enjoy it.

We had a good ratio of researchers who were experienced with the activity and those who were doing it for the first time. The number of volunteers was optimal for the number of visitors we had throughout the day. Everyone was busy but were able to take time for breaks throughout the day. Overall the event overall was a very positive experience for our researchers and a good opportunity for students to gain PE experience in a fun, relaxed atmosphere. It was also a good opportunity to engage with children who would not necessarily get the chance to attend a more formal science outreach event.

Stand visitors:
The stand was consistently busy throughout the 6-hour session with around 90 children plus adult guardians stopping by to try out the activity. We monitored the number of stall visitors we had by counting the number of bags we gave out and we predict that they spent approximately 10 minutes at a time at the stand, providing good opportunities for conversation, questions and discussion. Most of the children were primary school age (5-12 years old).

Feedback:
We used a sticker rating chart in order to assess the impact of participation as a positive learning experience from the children involved. We received positive feedback throughout the session but we were also able to glean interesting insights into the public perception of viruses. Some people commented that it was nice to have such a stall in amongst the other charity stands to give the children something to occupy them. One parent asked if we did school visits as her son's school would be interested in something like our activity.
Follow-up:

This was the first time we had attended the Rodeo and it was very successful. The activity was well received. We were well prepared for the volume of people we would have at the stand and had ample supplies with us. Unfortunately, we did not have access to enough t-shirts to hand out to all of the volunteers making it difficult for people to recognise who we were however we used the CVR printed lab coats instead which were very recognisable. It was felt that this stand was useful as it allowed us to do science outreach on our doorstep and would appeal to people who would not come along to a large science festival. A number of stall visitors asked if we had a collection tin so if the CVR returned in subsequent years we could maybe provide a charity tin to raise money for a chosen cause.
Year(s) Of Engagement Activity 2018
URL https://www.facebook.com/centreforvirusresearch/
 
Description MRC Festival - Classroom Takeover @ Cleveden Secondary School 14 June 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact As part of the MRC Festival, the CVR opted to run a session for higher biology pupils at a local secondary school. We approached one of the school teachers and following an initial discussion around what we could offer a date was agreed at the convenience of the school within the dates of the MRC Festival.
We used this as an opportunity to obtain funding to develop one existing activity and to develop a brand new idea devised by our bioinformaticians. The CVR Glovebox Challenge was an existing activity that involves performing a series of intricate tasks inside a portable glovebox chamber while wearing PPE. The game is designed to help describe the conditions that can be found inside a wet lab and to introduce conversations about life working within a busy, cutting-edge laboratory. The glovebox chamber was due to go back into commission so funding for the MRC Festival meant we could replace the item and make use of it during our activity and beyond at future events.

Biolegomatics
This was a new activity developed by CVR bioinformaticians as a way to help explain the basic principles of genetic sequencing while also encouraging discussions around the role of a computer/data scientist. This activity proved particularly popular given the recent introduction of bioinformatics to the secondary school curriculum.

Event preparation and format:
CVR researchers began preparing for the event first by attending a mentoring session with Steve Allman to help develop ideas. They then went on to meet up on a further two occasions to refine timings and format and also to have a practice run-through.
Our researchers structured the event by creating a story to explain the 5 key stages of research that follows a virus outbreak. Pupils were then divided into groups and each rotated round a series of 5 activities that helped to explain each of the 5 stages. We also planned to allow time for feedback at the end and took a quiz in case of any down time. In the event, we actually ran right up to the classroom bell.

Feedback:
We took feedback forms for the pupils and teachers to complete. Unfortunately, we ran out of time as the pupils were very engaged in the activities. We asked the teacher if he would ask the pupils to complete the forms in a later class. Unfortunately, this did not happen due to time constraints.
We did however, receive incredibly positive feedback from all 3 teachers present who all commented on how enthusiastic and engaged the pupils were in each of the activities. We have also had multiple follow-up contacts from the class teacher who reported that the pupils were '100% enthused' and he also reported that the biolegomatics activity had helped pupils when they came to covering bioinformatics later in the school year.

Follow-up:
We have remained in contact with the class teacher as above and he has also in return been in touch to enquire about work experience opportunities. For this we directed him to sources of information and support within the MVLS College. We have also approached the school to ask of their interest in bringing pupils to the CVR for a visit as part of our festival activity in 2019. As a result we hope to maintain a longer term relationship with the school and to meet with our objective of inspiring the future generation of scientists.
Year(s) Of Engagement Activity 2018
URL https://www.facebook.com/centreforvirusresearch/
 
Description MRC Parliamentary Event 6 February 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact The CVR participated in the MRC parliamentary event on 6 February 2019. This event was coordinated by the MRC Executive and was hosted by Lewis MacDonald MSP. Invitations were extended to all MSPs by the MRC. Richard Lochhead, Minister for Further Education, Higher Education and Science attended and gave a short speech. Cabinet Secretary for Health and Sport, Jeane Freeman also attended. From the CVR Alain Kohl, Claire Donald and Ben Brennan displayed at a stand with a poster, film clip of mosquitoes and augmented reality viruses with tablets. Massimo Palmarini and John McLauchlan attended as guests in the room. The CVR also extended the invitation to Vice Principal for Research Prof Miles Padgett, Dean for Research Prof Graeme Milligan and Head of Institute Prof Iain McInnes. In the run up to the event, the CVR followed up with 9 MSPs informing of our presence at the event. We received positive responses from Miles Briggs and Patrick Grady.
Year(s) Of Engagement Activity 2019
URL https://www.facebook.com/centreforvirusresearch/
 
Description March 2017 - Alain Kohl - Financial Times Interview 
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 Media (as a channel to the public)
Results and Impact In March 2017 Prof Alain Kohl was interviewed by the Financial Times on 10 March for commentary regarding the impact of Brexit on science research. We are not aware of any articles or impact.
Year(s) Of Engagement Activity 2017
 
Description March 2017 - Alain Kohl - New Scientist Interview 
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 Media (as a channel to the public)
Results and Impact In March 2017 Alain Kohl was interviewed for an article about Zika virus for the New Scientist - https://www.newscientist.com/article/mg23331164-400-warmer-weather-could-bring-fresh-zika-misery/ The aim was to share the work and expertise of his research group with a global audience via a high-profile publication. The article was also shared on CVR Facebook and Twitter channels for wider circulation.
Year(s) Of Engagement Activity 2017
URL https://www.facebook.com/centreforvirusresearch
 
Description March 2017 - Prime Minister Theresa May - Scottish News Conference 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact In March 2017 during a visit to Scotland Prime Minister Theresa May recognised and referenced the CVR's zika virus research programme during a news conference interview. we believe this was a result of our overall efforts to engage with politicians and extensive media engagement during 2016 and 2017.
Year(s) Of Engagement Activity 2017
URL https://www.facebook.com/centreforvirusresearch
 
Description Max Perutz Award 2018 - Stephanie Cumberworth 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact CVr PhD student Stephanie Cumberworth submitted an entry for the MRC Max Perutz Award 2018. The competition receives >1000 entries and Stephanie was successful to be among 10 shortlisted candidates for the prize. Stephanie attended a reception in London in October 2018. The competition is designed to allow PhD students to reach a wider audience with their research.
Year(s) Of Engagement Activity 2018
URL https://www.facebook.com/centreforvirusresearch/
 
Description Nov 2018 Stephanie Cumberworth Blog post 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact CVR Communications Officer Siobhan Petrie shared a blog post to highlight the success of Stephanie Cumberworth who was shortlisted for the MRC 2018 Max Perutz Award. The post contained Stephanie's article - The Zika virus and a brain in a dish: https://cvrblog.myportfolio.com/copy-of-the-zika-virus-and-the-brain-in-a-dish

https://cvrblog.myportfolio.com/copy-of-the-zika-virus-and-the-brain-in-a-dish

approx 61 page views
Year(s) Of Engagement Activity 2018
URL https://www.facebook.com/centreforvirusresearch/
 
Description November 2017 - Girlguiding Dunbartonshire Workshop 
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 In November 2017 a group of CVR researchers work with a local guide leader (and also a member of CVR staff) to arrange an evening workshop of interactive activities for a local Girlguide group. Through a mix of popular CVR activities, our team of researchers provided education about viruses, research and information about pursuing a successful science career. Since the event, a further session has taken place leading to two further requests for involvement with additional groups.
Year(s) Of Engagement Activity 2017
URL https://www.facebook.com/centreforvirusresearch/
 
Description October 2017 - Alain Kohl - Media Interview 
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 Media (as a channel to the public)
Results and Impact Prof Alain Kohl was interviewed for a Luxembourg-based online magazine - http://delano.lu/d/detail/news/celebrating-science-catching-virology-bug/160142
Year(s) Of Engagement Activity 2017
URL https://www.facebook.com/centreforvirusresearch
 
Description October 2017 - MoSSFest 
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 In October 2017 a group of CVR researchers took a stand at the Middle of Scotland Science Festival in Glasgow. Our team used a mix of Art Goes Viral colouring book and craft materials as well as Zika snakes and ladders and the glovebox chamber activity. This was a collaboration with the Welcome Trust Centre for Micro Parasitology and also an opportunity to provide a public engagement experience for a University of Glasgow undergraduate student. The team estimate that they engaged with approximately 150 children along with adult supervisors. One researcher also produced the evaluation report for the event. The activity was shared on Twitter using the festival hashtag.
Year(s) Of Engagement Activity 2017
URL https://www.facebook.com/centreforvirusresearch
 
Description October 2017 - Stephanie Cumberworth Skype a Scientist 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Schools
Results and Impact In October 2017 CVR PhD student Stephanie Cumberworth took part in the 'Skype a Scientist' initiative and skyped a school class based in Portugal. this was a chance for Stephanie to share her work, career path and for students to ask questions. Stephanie shared her experience on her personal twitter account, which was in turn retweeted.
Year(s) Of Engagement Activity 2017
URL https://twitter.com/88lfm88/status/923102558599643136
 
Description September 2017 - Claire Donald - The Conversation - Zika virus 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact In September 2017 CVR postdoc Dr Claire Donald produced an article about the status of the Zika virus outbreak for The Conversation - https://theconversation.com/whatever-happened-to-the-zika-virus-82618. The article was also shared on the CVR Facebook and Twitter pages gaining a reach of 690 contacts on Facebook alone along with shares and likes. Claire also engaged with a reader who posted a question on The Conversation website.
Year(s) Of Engagement Activity 2017
URL https://www.facebook.com/centreforvirusresearch
 
Description September 2017 - Explorathon 
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 In September 2017 a group of 8 CVR researchers led an exhibition of activities at the Explorathon event at the Glasgow Transport Museum. Our team showcased 3 CVR activities including the glovebox chamber activity, build a virus and zika snakes and ladders. This very busy event (over 3000 free tickets are distributed) attracted approximately 200 children accompanied by adults to the CVR stand. Images were shared on social media reaching 609 contacts on Facebook alone.
Year(s) Of Engagement Activity 2017
URL https://www.facebook.com/centreforvirusresearch
 
Description World Mosquito Day August 2018 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Undergraduate students
Results and Impact At the CVR, we carry out world-leading research on mosquito ecology & control, as well as working on mosquito-borne viruses such as Zika, Dengue and Chikungunya. To mark World Mosquito Day, Stephanie Rainey explains the importance of the CVR's Wolbachia programme, while Alain Kohl talks about the discovery of Zika virus. Both were interviewed by the UofG press team with interviews shared with >20K followers:

http://ow.ly/403i30ltuff

https://twitter.com/UofGMVLS/status/1031469005490532353

https://twitter.com/UofGMVLS/status/1031512634900865024
Year(s) Of Engagement Activity 2018
URL https://www.facebook.com/centreforvirusresearch