Developing a Vaccine to Block West Nile Virus Transmission: In Silico Studies, Molecular Characterization, Expression, and Blocking Activity of MosGCTL-1

Overview

Journal Pathogens

Date 2021 Mar 6

PMID 33671430

Citations 1

Authors

Hasan Bakhshi

Mehdi Fazlalipour

Javad Dadgar-Pakdel

Sedigheh Zakeri

Abbasali Raz

Anna-Bella Failloux

Navid Dinparast Djadid

Affiliations

Soon will be listed here.

Abstract

Background: Mosquito galactose-specific C-type lectins (mosGCTLs), such as mosGCTL-1, act as ligands to facilitate the invasion of flaviviruses like West Nile virus (WNV). WNV interacts with the of (Culicidae) and facilitates the invasion of this virus. Nevertheless, there is no data about the role of mosGCTL-1 as a transmission-blocking vaccine candidate in , the most abundant Culicinae mosquito in temperate regions.

Methods: Adult female mosquitoes were experimentally infected with a WNV infectious blood meal, and the effect of rabbit anti-rmosGCTL-1 antibodies on virus replication was evaluated. Additionally, in silico studies such as the prediction of protein structure, homology modeling, and molecular interactions were carried out.

Results: We showed a 30% blocking activity of polyclonal antibodies (compared to the 10% in the control group) with a decrease in infection rates in mosquitoes at day 5 post-infection, suggesting that there may be other proteins in the midgut of that could act as cooperative-receptors for WNV. In addition, docking results revealed that WNV binds with high affinity, to the mosquito lectin receptors.

Conclusions: Our results do not support the idea that mosGCTL-1 of primarily interacts with WNV to promote viral infection, suggesting that other mosGCTLs may act as primary infection factors in

Citing Articles

Recognition of Arboviruses by the Mosquito Immune System.

Prince B, Walsh E, Torres T, Ruckert C Biomolecules. 2023; 13(7).

PMID: 37509194 PMC: 10376960. DOI: 10.3390/biom13071159.

References

Murgue B, Murri S, Zientara S, Durand B, Durand J, Zeller H . West Nile outbreak in horses in southern France, 2000: the return after 35 years. Emerg Infect Dis. 2001; 7(4):692-6. PMC: 2631744. DOI: 10.3201/eid0704.010417. View

Fritz M, Walker E, Miller J, Severson D, Dworkin I . Divergent host preferences of above- and below-ground Culex pipiens mosquitoes and their hybrid offspring. Med Vet Entomol. 2015; 29(2):115-23. DOI: 10.1111/mve.12096. View

Liu N . Insecticide resistance in mosquitoes: impact, mechanisms, and research directions. Annu Rev Entomol. 2015; 60:537-59. DOI: 10.1146/annurev-ento-010814-020828. View

Weis W, Drickamer K, Hendrickson W . Structure of a C-type mannose-binding protein complexed with an oligosaccharide. Nature. 1992; 360(6400):127-34. DOI: 10.1038/360127a0. View

Hwang J, Jurado K, Fikrig E . Genetics of War and Truce between Mosquitos and Emerging Viruses. Cell Host Microbe. 2016; 19(5):583-7. PMC: 7063512. DOI: 10.1016/j.chom.2016.04.009. View

Guex N, Peitsch M, Schwede T . Automated comparative protein structure modeling with SWISS-MODEL and Swiss-PdbViewer: a historical perspective. Electrophoresis. 2009; 30 Suppl 1:S162-73. DOI: 10.1002/elps.200900140. View

Bertrand J, Pignol D, Bernard J, Verdier J, Dagorn J, Fontecilla-Camps J . Crystal structure of human lithostathine, the pancreatic inhibitor of stone formation. EMBO J. 1996; 15(11):2678-84. PMC: 450203. View

Tormo J, Natarajan K, Margulies D, Mariuzza R . Crystal structure of a lectin-like natural killer cell receptor bound to its MHC class I ligand. Nature. 1999; 402(6762):623-31. DOI: 10.1038/45170. View

Perera-Lecoin M, Meertens L, Carnec X, Amara A . Flavivirus entry receptors: an update. Viruses. 2014; 6(1):69-88. PMC: 3917432. DOI: 10.3390/v6010069. View

10.

Adelman Z, Myles K . The C-Type Lectin Domain Gene Family in and Their Role in Arbovirus Infection. Viruses. 2018; 10(7). PMC: 6070988. DOI: 10.3390/v10070367. View

11.

Tham H, Balasubramaniam V, Chew M, Ahmad H, Hassan S . Protein-protein interactions between A. aegypti midgut and dengue virus 2: two-hybrid screens using the midgut cDNA library. J Infect Dev Ctries. 2016; 9(12):1338-49. DOI: 10.3855/jidc.6422. View

12.

Weis W, Kahn R, Fourme R, Drickamer K, Hendrickson W . Structure of the calcium-dependent lectin domain from a rat mannose-binding protein determined by MAD phasing. Science. 1991; 254(5038):1608-15. DOI: 10.1126/science.1721241. View

13.

Selin L, Cornberg M, Brehm M, Kim S, Calcagno C, Ghersi D . CD8 memory T cells: cross-reactivity and heterologous immunity. Semin Immunol. 2004; 16(5):335-47. PMC: 7128110. DOI: 10.1016/j.smim.2004.08.014. View

14.

Cheng G, Cox J, Wang P, Krishnan M, Dai J, Qian F . A C-type lectin collaborates with a CD45 phosphatase homolog to facilitate West Nile virus infection of mosquitoes. Cell. 2010; 142(5):714-25. PMC: 2954371. DOI: 10.1016/j.cell.2010.07.038. View

15.

Mizuno H, Fujimoto Z, Koizumi M, Kano H, Atoda H, Morita T . Structure of coagulation factors IX/X-binding protein, a heterodimer of C-type lectin domains. Nat Struct Biol. 1997; 4(6):438-41. DOI: 10.1038/nsb0697-438. View

16.

Fernandez-Garcia M, Mazzon M, Jacobs M, Amara A . Pathogenesis of flavivirus infections: using and abusing the host cell. Cell Host Microbe. 2009; 5(4):318-28. DOI: 10.1016/j.chom.2009.04.001. View

17.

Boyington J, Riaz A, Patamawenu A, Coligan J, Brooks A, Sun P . Structure of CD94 reveals a novel C-type lectin fold: implications for the NK cell-associated CD94/NKG2 receptors. Immunity. 1999; 10(1):75-82. DOI: 10.1016/s1074-7613(00)80008-4. View

18.

Campbell-Lendrum D, Manga L, Bagayoko M, Sommerfeld J . Climate change and vector-borne diseases: what are the implications for public health research and policy?. Philos Trans R Soc Lond B Biol Sci. 2015; 370(1665). PMC: 4342958. DOI: 10.1098/rstb.2013.0552. View

19.

Pierson T, Xu Q, Nelson S, Oliphant T, Nybakken G, Fremont D . The stoichiometry of antibody-mediated neutralization and enhancement of West Nile virus infection. Cell Host Microbe. 2007; 1(2):135-45. PMC: 2656919. DOI: 10.1016/j.chom.2007.03.002. View

20.

Hamer G, Kitron U, Goldberg T, Brawn J, Loss S, Ruiz M . Host selection by Culex pipiens mosquitoes and West Nile virus amplification. Am J Trop Med Hyg. 2009; 80(2):268-78. View