Viruses of filarial worms- interactions with mosquito cells and endosymbionts

The 2024/25 application process is now closed

Visit the MRC DTP/CASE at LSTM pages for further information.

Abstract

The viral repertoire of filarial worms that are transmitted by mosquitoes has only recently been discovered and covers multiple viral families and orders. How and whether these viruses interact also with vector cells is a question of great interest, as these viruses could potentially replicate in vector cells and interact with these in different manners- outcomes that are positive for worms, neutral, or outcomes that are negative for worms. It is known for example that the STAT pathway can control worms in Aedes aegypti, but conversely viruses often target this pathway too. Thus, viruses could potentially benefit survival and propagation of worms if they target mosquito pathways. Viruses do not necessarily have to replicate to achieve this as long as specific proteins are expressed, but replication in mosquito cells can be easily investigated through induction mosquito RNAi responses or other host responses, which in itself would be relevant as it would allow targeting of viral gene expression with effects on worms verifiable at the same time. Furthermore, it is known that several medically important filarial worms harbour a Wolbachia endosymbiont that is crucial for nematode development and transmission3. While this endosymbiont is known to infect many species of insects, including vectors of disease, and can suppress the replication of pathogenic viruses4, it is unknown whether a similar phenotype is induced by Wolbachia in filarial worms. Investigations into this web of interactions are highly unique and rely on the specific expertise present at LSTM. This project could lead to entirely novel targeting strategies against transmission of filarial nematodes via their viruses and vectors, giving novel insight into interactions with the vector-especially in regard to whether these viruses infect vectors, and might be transmitted alongside worms or exclusively with worms to vertebrate hosts.

Where does the project lie on the Translational Pathway?

T1 – Basic Research

Expected Outputs
  • Data on the virus-host interactions in a very unique and novel setting
  • Contribution of host interactors on virus replication and virus life cycle.
  • Information on whether these interactions have biological outcomes that impact mosquito cell-virus interactions, and mosquito cell-filarial worm interactions.
  • Publications expected.

 

Training Opportunities

Conferences & seminars; small/genomics data analysis and statistics, usage of bioinformatic programs and the Linux environment, microscopy (Fluorescent In-Situ Hybridisation, FISH).

Skills Required

Basic understanding of virus replication and parasitology; some skills in cell culture and molecular biology.

Key Publications associated with this project

Gestuveo, R. J., J. Royle, C. L. Donald, D. J. Lamont, E. C. Hutchinson, A. Merits, A. Kohl* **, M. Varjak*. Analysis of Zika capsid-Aedes aegypti mosquito interactome reveals pro-viral host factors critical for establishing infection. Nature Communications 12: 2766. 2021.

*Co-corresponding authors, **Lead contact

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. 2022.

Quek, S.*, Cook, D. A. C.*, Wu, Y.*, Marriott, A. E., Steven, A., Johnston, K. L., Ford, L., Archer, J., Hemingway, J.**, Ward, S. A., Wagstaff, S. C., Turner, J. D., Taylor, M. J.** Wolbachia depletion blocks transmission of lymphatic filariasis by preventing chitinase-dependent parasite exsheathment. Proceedings of the National Academy of Sciences 119(15): e2120003119. 2022.

*Contributed equally. **Co-corresponding authors.

Taylor MJ, Bordenstein SR, Slatko B. Microbe Profile: Wolbachia: a sex selector, a viral protector and a target to treat filarial nematodes. Microbiology 164(11): 1345-1347. 2018.

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. 2022.