Current Understanding of the Molecular Basis of Venezuelan Equine Encephalitis Virus Pathogenesis and Vaccine Development

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2019 Feb 21

PMID 30781656

Citations 44

Authors

Anuj Sharma

Barbara Knollmann-Ritschel

Affiliations

Soon will be listed here.

Abstract

Venezuelan equine encephalitis virus (VEEV) is an alphavirus in the family Togaviridae. VEEV is highly infectious in aerosol form and a known bio-warfare agent that can cause severe encephalitis in humans. Periodic outbreaks of VEEV occur predominantly in Central and South America. Increased interest in VEEV has resulted in a more thorough understanding of the pathogenesis of this disease. Inflammation plays a paradoxical role of antiviral response as well as development of lethal encephalitis through an interplay between the host and viral factors that dictate virus replication. VEEV has efficient replication machinery that adapts to overcome deleterious mutations in the viral genome or improve interactions with host factors. In the last few decades there has been ongoing development of various VEEV vaccine candidates addressing the shortcomings of the current investigational new drugs or approved vaccines. We review the current understanding of the molecular basis of VEEV pathogenesis and discuss various types of vaccine candidates.

Citing Articles

Long-Term Protection in Atlantic Salmon () to Pancreas Disease (PD) Can Be Achieved Through Immunization with Genetically Modified, Live Attenuated Salmonid Alphavirus 3.

Braaen S, Wessel O, Bjorgen H, Rimstad E Vaccines (Basel). 2025; 13(2).

PMID: 40006736 PMC: 11861613. DOI: 10.3390/vaccines13020190.

Neuropathogenesis of Encephalitic Alphaviruses in Non-Human Primate and Mouse Models of Infection.

Woodson C, Carney S, Kehn-Hall K Pathogens. 2025; 14(2).

PMID: 40005568 PMC: 11858634. DOI: 10.3390/pathogens14020193.

Single-cell and spatiotemporal transcriptomic profiling of brain immune infiltration following Venezuelan equine encephalitis virus infection.

Rangel M, Sebastian A, Leon N, Phillips A, Gorman B, Hum N Front Immunol. 2025; 15:1497839.

PMID: 39749347 PMC: 11693676. DOI: 10.3389/fimmu.2024.1497839.

Neurological manifestations of encephalitic alphaviruses, traumatic brain injuries, and organophosphorus nerve agent exposure.

VanderGiessen M, de Jager C, Leighton J, Xie H, Theus M, Johnson E Front Neurosci. 2024; 18:1514940.

PMID: 39734493 PMC: 11671522. DOI: 10.3389/fnins.2024.1514940.

A multi-epitope self-amplifying mRNA SARS-CoV-2 vaccine design using a reverse vaccinology approach.

Claudia B, Nugrahapraja H, Giri-Rachman E Res Pharm Sci. 2024; 19(5):520-548.

PMID: 39691299 PMC: 11648349. DOI: 10.4103/RPS.RPS_91_23.

References

Schonbeck U, Mach F, Libby P . Generation of biologically active IL-1 beta by matrix metalloproteinases: a novel caspase-1-independent pathway of IL-1 beta processing. J Immunol. 1998; 161(7):3340-6. View

ARONSON J, Grieder F, Davis N, Charles P, Knott T, Brown K . A single-site mutant and revertants arising in vivo define early steps in the pathogenesis of Venezuelan equine encephalitis virus. Virology. 2000; 270(1):111-23. DOI: 10.1006/viro.2000.0241. View

Schoneboom B, Fultz M, MILLER T, MCKINNEY L, Grieder F . Astrocytes as targets for Venezuelan equine encephalitis virus infection. J Neurovirol. 1999; 5(4):342-54. DOI: 10.3109/13550289909029475. View

Bounds C, Terry F, Moise L, Hannaman D, Martin W, De Groot A . An immunoinformatics-derived DNA vaccine encoding human class II T cell epitopes of Ebola virus, Sudan virus, and Venezuelan equine encephalitis virus is immunogenic in HLA transgenic mice. Hum Vaccin Immunother. 2017; 13(12):2824-2836. PMC: 5718811. DOI: 10.1080/21645515.2017.1329788. View

Williams A, OBrien L, Phillpotts R, Perkins S . Improved efficacy of a gene optimised adenovirus-based vaccine for venezuelan equine encephalitis virus. Virol J. 2009; 6:118. PMC: 2732613. DOI: 10.1186/1743-422X-6-118. View

Schoneboom B, Lee J, Grieder F . Early expression of IFN-alpha/beta and iNOS in the brains of Venezuelan equine encephalitis virus-infected mice. J Interferon Cytokine Res. 2000; 20(2):205-15. DOI: 10.1089/107999000312621. View

Davis N, Powell N, Greenwald G, Willis L, Johnson B, Smith J . Attenuating mutations in the E2 glycoprotein gene of Venezuelan equine encephalitis virus: construction of single and multiple mutants in a full-length cDNA clone. Virology. 1991; 183(1):20-31. DOI: 10.1016/0042-6822(91)90114-q. View

Johnston R, Smith J . Selection for accelerated penetration in cell culture coselects for attenuated mutants of Venezuelan equine encephalitis virus. Virology. 1988; 162(2):437-43. DOI: 10.1016/0042-6822(88)90484-9. View

Vogel P, Abplanalp D, Kell W, Ibrahim M, Downs M, Pratt W . Venezuelan equine encephalitis in BALB/c mice: kinetic analysis of central nervous system infection following aerosol or subcutaneous inoculation. Arch Pathol Lab Med. 1996; 120(2):164-72. View

10.

HART M, Pratt W, Panelo F, Tammariello R, Dertzbaugh M . Venezuelan equine encephalitis virus vaccines induce mucosal IgA responses and protection from airborne infection in BALB/c, but not C3H/HeN mice. Vaccine. 1997; 15(4):363-9. DOI: 10.1016/s0264-410x(96)00204-6. View

11.

Perkins S, OBrien L, Phillpotts R . Boosting with an adenovirus-based vaccine improves protective efficacy against Venezuelan equine encephalitis virus following DNA vaccination. Vaccine. 2006; 24(17):3440-5. DOI: 10.1016/j.vaccine.2006.02.020. View

12.

Cain M, Salimi H, Gong Y, Yang L, Hamilton S, Heffernan J . Virus entry and replication in the brain precedes blood-brain barrier disruption during intranasal alphavirus infection. J Neuroimmunol. 2017; 308:118-130. PMC: 5694394. DOI: 10.1016/j.jneuroim.2017.04.008. View

13.

Paessler S, Weaver S . Vaccines for Venezuelan equine encephalitis. Vaccine. 2009; 27 Suppl 4:D80-5. PMC: 2764542. DOI: 10.1016/j.vaccine.2009.07.095. View

14.

Volkova E, Gorchakov R, Frolov I . The efficient packaging of Venezuelan equine encephalitis virus-specific RNAs into viral particles is determined by nsP1-3 synthesis. Virology. 2005; 344(2):315-27. PMC: 2430184. DOI: 10.1016/j.virol.2005.09.010. View

15.

Kolokoltsov A, Fleming E, Davey R . Venezuelan equine encephalitis virus entry mechanism requires late endosome formation and resists cell membrane cholesterol depletion. Virology. 2006; 347(2):333-42. DOI: 10.1016/j.virol.2005.11.051. View

16.

Guerbois M, Volkova E, Forrester N, Rossi S, Frolov I, Weaver S . IRES-driven expression of the capsid protein of the Venezuelan equine encephalitis virus TC-83 vaccine strain increases its attenuation and safety. PLoS Negl Trop Dis. 2013; 7(5):e2197. PMC: 3649961. DOI: 10.1371/journal.pntd.0002197. View

17.

Brandstadter J, Yang Y . Natural killer cell responses to viral infection. J Innate Immun. 2011; 3(3):274-9. PMC: 3128146. DOI: 10.1159/000324176. View

18.

Garoff H, Hewson R, Opstelten D . Virus maturation by budding. Microbiol Mol Biol Rev. 1998; 62(4):1171-90. PMC: 98943. DOI: 10.1128/MMBR.62.4.1171-1190.1998. View

19.

Saxena M, Van T, Baird F, Coloe P, Smooker P . Pre-existing immunity against vaccine vectors--friend or foe?. Microbiology (Reading). 2012; 159(Pt 1):1-11. PMC: 3542731. DOI: 10.1099/mic.0.049601-0. View

20.

Reed D, Lind C, Lackemeyer M, Sullivan L, Pratt W, Parker M . Genetically engineered, live, attenuated vaccines protect nonhuman primates against aerosol challenge with a virulent IE strain of Venezuelan equine encephalitis virus. Vaccine. 2005; 23(24):3139-47. DOI: 10.1016/j.vaccine.2004.12.023. View