| Abstract | Protozoan parasites such as Leishmania are important causes of human disease, but they themselves can be infected by viruses. This emerging field in infectious diseases bridges parasitology and virology, and importantly the presence of virus may also modulate human disease through viral stimulation of immunity, promotion of parasite entry into immune cells etc. There is hence important scope to study these interactions. This project will focus on Leishmania martiniquensis and its endogenous bunyavirus. The genome of bunyaviruses consists of three strands of negative stranded RNA called L, M and S. The genome termini interact for the genomes to form circular structures. Importantly, these interacting termini also contain sequences that direct replication and transcription of the viral genomes. Intriguingly, and unlike for other bunyaviruses that infect animals and plants, inversion in the terminal sequences of the M segment (which encodes -presumably- a single viral glycoprotein, as opposed to two in other bunyaviruses required for receptor binding and entry) have been observed. We will use reverse genetics approaches to assess the importance of these sequences and inversions in viral gene expression, and the role(s) of the protein encoded by the M segment. Thus, this bunyavirus of L. martiniquensis may allow us to investigate completely novel aspects of how these pathogens can replicate and propagate in protozoan hosts, and modulate parasite biology; moreover we will use cell biology and proteomics approaches to assess how the presumed glycoprotein functions to promote infection of the protozoan. We will also assess how the presence or absence of the virus of this M segment protein may impact infection of vertebrate cells such as human immune cells, and whether this virus has the potential to replicate in such cells and thus constitute potentially a protozoan borne virus- opening doors to a completely new research area both in fundamental biology, but also in understanding disease. |
| Where does this project lie in the translational pathway? | T1 - Basic Research |
| Expected Outputs | The project touches on highly novel aspects of virology in the field of virus-parasite interactions, which we expect to publish in high impact factor journals. It may open a completely new area of parasitology and virology, and thus allow for innovative funding applications that can touch on fundamental or medical aspects. |
| Training Opportunies | Beyond the project itself, the student will be encouraged to attend seminars or workshops relating to scientific aspects such as data analysis or technologies; moreover conference attendance and presentation of data are a key part of doctoral training. |
| Skills Required | Basic cell culture and molecular skills are advantageous. |
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Key Publications associated with this project |
Quek S., A. Hadermann, Y. Wu, L. De Coninck, S. Hegde, J. R. Boucher, J. Cresswell, E. Foreman, A. Steven, E. J. LaCourse, S. A. Ward, S. Wanji, G. L. Hughes, E. I. Patterson, S. C. Wagstaff, J. D. Turner, R. H. Parry, A. Kohl, E. Heinz, J. Matthijnssens, R. Colebunders, M. J. Taylor. Diverse RNA viruses of parasitic nematodes can elicit antibody responses in vertebrate hosts. Nature Microbiology (in press). |
| Alexander A. J. T., M. Salvemini, V. B. Sreenu, J. Hughes, E. L. Telleria, M. Ratinier, F. Arnaud, P. Volf, B. Brennan, A. Kohl. Characterisation of the antiviral RNA interference response to Toscana virus in sand fly cells. PLOS Pathogens 19(3): e1011283. 2023. | |
| Gestuveo R. J., R. Parry, L. B. Dickson, S. Lequime, V. B. Sreenu, M. J. Arnold, A. A. Khromykh, E. Schnettler, L. Lambrechts, M. Varjak, A. Kohl. Mutational analysis of Aedes aegypti Dcr2 provides insights into the biogenesis of antiviral exogenous small interfering RNAs. PLOS Pathogens 18(1): e1010202. 2022. |