RiftVectors: Vector competence of European mosquitoes to Rift Valley fever virus

Lead Research Organisation: Lancaster University
Department Name: Division of Biomedical and Life Sciences

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 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 The objective of this project has been to assess the capacity of different strains of Wolbachia bacteria to cause transmission blocking of Rift Valley Fever and other arboviruses in vector mosquitoes. This has involved experimental assessment of Wolbachia-host interactions both in a tissue culture system in vitro, and attempts to generate somatic and heritable transinfections in vivo.
We have successfully generated model of Wolbachia transinfection in a tissue culture system by transinfecting cells of the mosquito species Culex quinquefasciatus with Wolbachia strains, including a high-density member of Wolbachia supergroup A called wAu that naturally infects the fruit fly species Drosophila simulans.
We generated several stable and heritable transinfections of non-native Wolbachia strains in Culex quinquefasciatus. The wAlbB strain transferred from Aedes albopictus produces a medium-density transinfection, similar to overall density of the naturally occurring wPIp strain of Wolbachia in Culex but with higher dissemination to somatic tissues such as the midgut. This line has been challenged with RVFV and West Nile Virus and although titres were somewhat reduced, they were still able to transmit. However the wAlbA strain, also transferred from Ae. albopictus, forms a much higher density transinfection than wAlbB or wPip (over tenfold greater overall with very high somatic densities). Bidirectional cytoplasmic incompatibility (CI) is generated with the wild type wPip-carrying line.
Five Wolbachia-transinfected lines of Ae. aegypti have been created and characterised including virus challenges; the Wolbachia strain wAu produced the most efficient transmission blocking of all those tested, and was also found to show relatively stable maternal transmission under high temperature larval treatment, and to produce only moderate fitness costs to the host. This work is currently under review at PNAS.
Exploitation Route The findings will be of interest to those seeking to utilise novel Wolbachia-based disease control strategies for arboviruses including dengue and Zika, and also to those interested in conservation as Culex are major vector of avian malaria.
Sectors Environment,Healthcare

 
Description One of the lines we generated of Aedes aegypti mosquitoes carrying Wolbachia (strain wAlbB), to which this funding contributed, has been used in field trials in Kuala Lumpur, Malaysia which have reduced dengue transmission in 6 release areas by up to 80%. As a result the Malaysian Ministry of Health is now rolling out the strategy on a larger scale for dengue control.
First Year Of Impact 2019
Sector Healthcare
Impact Types Societal

 
Description Collaboration on Rift Valley Fever 
Organisation University of Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution Exchange of cell lines and reciprocal research visits
Collaborator Contribution Exchange of Culex mosquito cell lines, advice and assistance with virus challenges
Impact no publications or other outputs yet
Start Year 2012
 
Description Collaboration on Rift Valley Fever Vectors 
Organisation Pasteur Institute, Paris
Country France 
Sector Charity/Non Profit 
PI Contribution We are collaborating on vectors of Rift Valley fever, to include viral challenge of mosquito lines transinfected with Wolabchia, and sharing of cell lines
Collaborator Contribution Challenge of mosquito lines and cell lines generated in lancaster with viruses
Impact not publications or other outputs yet
Start Year 2012