Targeted inhibition of Rift Valley Fever Virus
Lead Research Organisation:
THE PIRBRIGHT INSTITUTE
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
Rift valley fever virus (RVFV), Bunyaviridae, is a zoonotic arbovirus that causes disease in ruminants and humans. Protection is afforded by vaccination however; current vaccines induce complications in livestock. Together with the outbreak potential, the lack of prophylaxis makes RVFV a serious public health concern. Innovative ways to create safe vaccines are needed that will induce lifelong immunity in the animal host and be non-transmissible by arthropod vectors. An upcoming field in antiviral research involves microRNAs (miRNA) which may inhibit viral replication in vitro or restrict cellular tropism for a variety of viruses.
Within efforts to generate genetically modified RVFV vaccines, miRNA targets that are conserved within Aedes mosquito cell lines will be chosen for targeted inhibition of RVFV. Selection criteria for miRNAs include high copy number in each cell line and insect specificity. Constructs containing selected miRNA targets will be cloned into the SVF4 genome to establish the knockdown efficacy of virus replication in different cell lines. miRNA targets showing greatest efficacy will be cloned into the NSs region of the S-segment of RVFV, allowing for the characterization of recombinant RVFV in various mosquito and vertebrate cell lines and define the host range of these viruses in live mosquitoes.
Within efforts to generate genetically modified RVFV vaccines, miRNA targets that are conserved within Aedes mosquito cell lines will be chosen for targeted inhibition of RVFV. Selection criteria for miRNAs include high copy number in each cell line and insect specificity. Constructs containing selected miRNA targets will be cloned into the SVF4 genome to establish the knockdown efficacy of virus replication in different cell lines. miRNA targets showing greatest efficacy will be cloned into the NSs region of the S-segment of RVFV, allowing for the characterization of recombinant RVFV in various mosquito and vertebrate cell lines and define the host range of these viruses in live mosquitoes.
Planned Impact
unavailable
Organisations
People |
ORCID iD |
| Rennos Fragkoudis (Principal Investigator) |
Publications
Bell-Sakyi L
(2016)
Microscopic Visualisation of Zoonotic Arbovirus Replication in Tick Cell and Organ Cultures Using Semliki Forest Virus Reporter Systems.
in Veterinary sciences
Ferguson MC
(2015)
Ability of the Encephalitic Arbovirus Semliki Forest Virus To Cross the Blood-Brain Barrier Is Determined by the Charge of the E2 Glycoprotein.
in Journal of virology
Rückert C
(2014)
Antiviral responses of arthropod vectors: an update on recent advances.
in Virusdisease
Rückert C
(2014)
Antiviral responses of arthropod vectors: an update on recent advances.
in Virusdisease
Schnettler E
(2013)
Knockdown of piRNA pathway proteins results in enhanced Semliki Forest virus production in mosquito cells.
in The Journal of general virology
Van Knippenberg I
(2013)
The transient nature of Bunyamwera orthobunyavirus NSs protein expression: effects of increased stability of NSs protein on virus replication.
in PloS one
| Description | By high throughput sequencing, we determined the transcriptome and the miRNAs, of the Asian Tiger Mosquito (Aedes albopictus). We then used these to engineer viruses that would be targetted by these miRNAs with the aim of generating viruses unable to replicate in arthropod cells but capable of replicating in mammalian cells. Using Semliki Forest virus and Rift valley fever virus, we showed this to be the case. |
| Exploitation Route | This proof of principle research could be exploited to design live attenuated vaccines for arbovirus diseases which are unable to be transmitted by mosquitoes. |
| Sectors | Pharmaceuticals and Medical Biotechnology |
| Description | The fundamental knowledge obtained in this research project is contributing to the design of new arbovirus vaccines. This has the potential to contribute to human and animal health, and thus food security, in many regions of the world. |
| First Year Of Impact | 2014 |
| Description | Invited seminar at the University of Nottingham seminar series |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Professional Practitioners |
| Results and Impact | An invited seminar entitled: "Arbovirus encephalitis: from tissue culture, to mosquitoes to mice" was delivered. Discussions for potential collaborations followed. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Invited seminar in Public Health England- Porton Down |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited seminar entitled: "Innate immune responses and pathogenesis of alphavirus infections". Numerous questions were asked and requests for collaborations were made. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Invited speaker at 9th Neuroinfections Conference, Bialowieza - Poland |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | An invited presentation entitled: "Using small RNAs to fight encephalitic arboviruses" was delivered. The presentation generated a lot of interest and questions. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Invited speaker at 9th Neuroinfections Conference, Bialowieza - Poland |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | An invited talk entitled: "Using small RNAs to fight encephalitic arboviruses" was delivered. Numerous questions were asked. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Invited speaker at South Wilts Virus Group (SWVG) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Professional Practitioners |
| Results and Impact | A talk entitled: "The role of small RNAs in arbovirus infections". Multiple questions were asked and potential for collaborations was identified. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Invited speaker at a workshop on arboviruses and their vectors in University of Malaya - Malaysia |
| 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 | A talk entitled: " The role of small RNAs in arbovirus infections" was delivered. Multiple questions and requests for collaborations followed the presentation. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Malaysia workshop |
| 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 | Organised and participated in workshop on genetic control of mosquitoes, primarily focusing on refractory methods. Included a set of open lectures from international speakers at University of Malaysia and more focus workshop-style meetings. Several reported changes to research activities and also opinions, also follow-up meeting organized in Glasgow later in 2017 |
| Year(s) Of Engagement Activity | 2017 |