Vector competence of European mosquitoes to Rift Valley fever virus

Lead Research Organisation: University of Glasgow
Department Name: College of Medical, Veterinary &Life Sci

Abstract

RVFV is an arbovirus readily transmitted through several mosquito genera including Aedes and Culex
mosquito vectors, and has a large host range. The recent expansion of the geographical range of RVFV
clearly indicates that RVFV is not restricted to Africa. It has been proposed that a single infected person
or animal that enters a naive country is sufficient to initiate an outbreak. This transmission scenario is
becoming more probable due to the expansion of worldwide trade and travel. The objectives of this
Emida project, RiftVectors, will be to understand the biology of natural RVFV vectors and their counterparts in
Europe as an indicator for assessing the risk of RVFV to be established in Europe.
Within this Emida project, we will further analyze, and develop new methods to distinguish mosquito vector and
potential vector species, and analyze whether they can transmit RVFV- especially european mosquitoes which
may be able to transmit RVFV. We will also analyze how the immune system of mosquito vectors can control RVFV
infection, and how this relates to whether mosquitoes can transmit RVFV or whether novel antiviral targets
can be discovered. Interestingy, endosymbiotic Wolbachia bacteria of insects now are widely used in symbiosis-based
control strategies against arboviruses. We will analyze what the effect of Wolbachia on the vector competence of mosquitoes
to RVFV will be, and if this could be used as a control strategy against this virus.
Our international consortium of partners has the expertise to tackle these questions on the
vectors of RVFV. We expect that our results will improve assessments of when and which
mosquito species could spread RVFV, and we aim to identify novel ways of controlling
RVFV emergence.

Technical Summary

This Emida project, RiftVectors, will address topics relating to arthropod vectors of RVFV. Firstly, we will improve methods for identification of RVFV vectors (with special focus on European counterparts of tropical mosquito species) through the use of molecular tools, and the
provision of quantitative estimates of species dynamics in European areas with potential RVFV vectors. Secondly, we aim to gain further insights into the competence of potential RVFV vectors, especially that of potential European vectors in comparison to their African counterparts; we will experimentally asses whether RVFV can adapt to European mosquitoes, and determine environmental factors influencing
maintenance and vertical transmission. Thirdly, we will study the induction and nature of innate immune responses of RVFV vectors, followed
by investigations on how these host responses control RVFV replication. Finally, we will carry out a detailed investigation whether, and if so how, Wolbachia bacteria can be used to inhibit RVFV replication and transmission in vector mosquitoes, as has been shown for other
arboviruses.

These questions will be addressed by five work packages. Two partners will be based in the UK (University of Oxford, MRC-University of Glasgow Centre for Virus Research).

Planned Impact

RVFV is an arbovirus maintained within an enzootic cycle between zoophilic mosquitoes and a variety of wild animals. Infection
causes severe and often fatal illness in sheep and cattle. RVFV has been isolated from at least
30 mosquito species, mostly Aedes and Culex. The probability of RVFV emerging in virgin
areas is likely to be increasing. This could involve territories near or within Europe, as well as trading partners.
Besides climate change which could affect the biology of vectors and their geographical distribution, increases of
international trade of livestock and human movements could lead to the introduction of RVFV in regions where susceptible hosts
and suitable vector mosquitoes reside. Indeed, the geographical range of RVFV has extended
over the past 10 years. More than 30 mosquito species have been found to be naturally
infected by RVFV including Aedes, Anopheles, Culex, Eretmapodites and Mansonia, and by
other vectors including sand flies. It has been proposed that a single infected person or
animal (live or dead) that enters a naive country is sufficient for the initiation of a major
outbreak before RVFV would ever be detected. This would have a major impact on animal and public health.
The biology of RVFV/vector interactions as well as the biology of vectors and potential RVFV vectors are poorly
understood and more research in this area is required to inform policy,
assess risk and develop novel control strategies.
 
Description This part of the RiftVectors project aims to elucidate the role of host responses in mosquitoes in controlling Rift Valley fever virus. We have carried out a full analysis of the antiviral response in mosquitos and the fruit fly model, and characterised a number of properties also in cell culture also. We characterised individual aspects of these responses further across these insect systems and obtained new and important insights into how RNAi pathways specifically control this important pathogen. We also expanded our work to other bunayviruses with cell culture studies. Note: this concerns only our section of the project.
Exploitation Route Findings are generally relevant for the field of vector antiviral RNAi responses; small RNA sequence information generated will also be useful to the wider community. Information and data on RVFV immune responses in vectors are likely to influence other researchers in the arbovirus or arthropod immunity field.
Sectors Agriculture, Food and Drink,Other

URL http://www.bioinformatics.cvr.ac.uk/RiftVector/index.php
 
Description Bunyavirus-host interactions and replication 
Organisation University of Glasgow
Department MRC - University of Glasgow Centre for Virus Research
Country United Kingdom 
Sector Academic/University 
PI Contribution Arthropod innate immunity reagents and expertise; bunyavirus expertise and reagents including viruses and infectious clones; experimental design and data evaluation.
Collaborator Contribution Bunyavirus expertise and reagents including viruses, infectious clones, minireplicon systems, protein expression clones; experimental design and data evaluation. With Professor Richard M. Elliott until he passed away in 2015 and currently with Dr Benjamin Brennan.
Impact Publications as listed with the relevant awards; novel infectious clones and minireplicon systems for specific bunyaviruses and new functional data on bunyavirus proteins, bunyavirus replication, bunyavirus-host interactions including immunity.
Start Year 2013
 
Description Insect immune responses to Rift Valley fever virus 
Organisation Bernhard Nocht Institute for Tropical Medicine
Country Germany 
Sector Hospitals 
PI Contribution Innate immunity expertise; reagents; experimental design and data evaluation.
Collaborator Contribution Arthropod biology and innate immunity expertise; in vivo infection systems; experimental design and data evaluation. With Dr Stefanie Muller; initially BNITM then TiHO.
Impact Innate immunity data for Rift Valley fever virus infection across multiple insect systems. One publication resulted from this interaction: https://www.ncbi.nlm.nih.gov/pubmed/28497117
Start Year 2012
 
Description Insect immune responses to Rift Valley fever virus 
Organisation University of Veterinary Medicine Hanover
PI Contribution Innate immunity expertise; reagents; experimental design and data evaluation.
Collaborator Contribution Arthropod biology and innate immunity expertise; in vivo infection systems; experimental design and data evaluation. With Dr Stefanie Muller; initially BNITM then TiHO.
Impact Innate immunity data for Rift Valley fever virus infection across multiple insect systems. One publication resulted from this interaction: https://www.ncbi.nlm.nih.gov/pubmed/28497117
Start Year 2012
 
Description Mosquito-arbovirus interactions 
Organisation Pasteur Institute, Paris
Country France 
Sector Academic/University 
PI Contribution Arboviruses and innate immunity expertise; experimental design and data evaluation.
Collaborator Contribution Mosquito infection systems; experimental design and data evaluation. With Dr Anna-Bella Failloux.
Impact Publications as listed with relevant awards; key interactions also within RiftVectors as well as Horizon 2020 Zikalliance and Infravec-2 consortia through taking lead of work packages and tasks given our combined expertise in the field at European level.
Start Year 2011
 
Description RiftVectors EMIDA-ERA NET consortium 
Organisation Experimental Zooprofilattico Institute of Lazio and Tuscany
Country Italy 
Sector Public 
PI Contribution Kohl leads the the RiftVectors consortium, which studies the vectors of Rift Valley fever. This includes partners in the UK, France and Italy. Subcontractors are located in Italy and Senegal. Associated partners of the RiftVectors consortium are based in Germany and the UK.
Collaborator Contribution We interact on several the work packages, and CVR/Kohl leads one of the work packages.
Impact Three original papers published: https://www.ncbi.nlm.nih.gov/pubmed/28497117 https://www.ncbi.nlm.nih.gov/pubmed/28060823 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761212/
Start Year 2012
 
Description RiftVectors EMIDA-ERA NET consortium 
Organisation Lancaster University
Country United Kingdom 
Sector Academic/University 
PI Contribution Kohl leads the the RiftVectors consortium, which studies the vectors of Rift Valley fever. This includes partners in the UK, France and Italy. Subcontractors are located in Italy and Senegal. Associated partners of the RiftVectors consortium are based in Germany and the UK.
Collaborator Contribution We interact on several the work packages, and CVR/Kohl leads one of the work packages.
Impact Three original papers published: https://www.ncbi.nlm.nih.gov/pubmed/28497117 https://www.ncbi.nlm.nih.gov/pubmed/28060823 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761212/
Start Year 2012
 
Description RiftVectors EMIDA-ERA NET consortium 
Organisation Pasteur Institute, Paris
Country France 
Sector Academic/University 
PI Contribution Kohl leads the the RiftVectors consortium, which studies the vectors of Rift Valley fever. This includes partners in the UK, France and Italy. Subcontractors are located in Italy and Senegal. Associated partners of the RiftVectors consortium are based in Germany and the UK.
Collaborator Contribution We interact on several the work packages, and CVR/Kohl leads one of the work packages.
Impact Three original papers published: https://www.ncbi.nlm.nih.gov/pubmed/28497117 https://www.ncbi.nlm.nih.gov/pubmed/28060823 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761212/
Start Year 2012
 
Description miRNA targeted arboviruses for vaccine design 
Organisation The Pirbright Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Design of miRNA containing Rift Valley fever and Semliki Forest viruses for mosquito infections.
Collaborator Contribution Production of miRNA target containing viruses, mosquito cell and mosquito infections. This collaboration began at the Roslin Institute, University of Edinburgh and continued at The Pirbright Institute with Professor John Fazakerley and Dr Rennos Fragkoudis though Ms Stacey Human's PhD thesis; Dr Fragkoudis currently continues the project.
Impact miRNA-targeted Semliki Forest viruses that showed differential replication in mosquito cells; miRNA-targeted Rift Valley fever viruses that remain to be fully characterised.
Start Year 2012
 
Description RiftVectors Website 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Website went live in 2014 and is still online; aimed at scientists or those involved in science/scientific decision making, general public etc on activities of the network and studies carried out.
Year(s) Of Engagement Activity 2014
URL http://www.bioinformatics.cvr.ac.uk/RiftVector/index.php