scholarly journals A Single-Site Mutant and Revertants Arising in Vivo Define Early Steps in the Pathogenesis of Venezuelan Equine Encephalitis Virus

Virology ◽  
2000 ◽  
Vol 270 (1) ◽  
pp. 111-123 ◽  
Author(s):  
Judith F. Aronson ◽  
Franziska B. Grieder ◽  
Nancy L. Davis ◽  
Peter C. Charles ◽  
Travis Knott ◽  
...  
Keyword(s):  
Venezuelan Equine Encephalitis Virus ◽  
Encephalitis Virus ◽  
Single Site ◽  
Venezuelan Equine Encephalitis ◽  
Equine Encephalitis Virus

scholarly journals Replication and Clearance of Venezuelan Equine Encephalitis Virus from the Brains of Animals Vaccinated with Chimeric SIN/VEE Viruses

2006 ◽  
Vol 80 (6) ◽  
pp. 2784-2796 ◽  
Author(s):  
Slobodan Paessler ◽  
Haolin Ni ◽  
Olga Petrakova ◽  
Rafik Z. Fayzulin ◽  
Nadezhda Yun ◽  
...  
Keyword(s):  
Venezuelan Equine Encephalitis Virus ◽  
Encephalitis Virus ◽  
Venezuelan Equine Encephalitis ◽  
Challenge Virus ◽  
Equine Encephalitis Virus ◽  
Adult Mice ◽  
The Central Nervous System ◽  
Different Strains

ABSTRACT Venezuelan equine encephalitis virus (VEEV) is an important, naturally emerging zoonotic pathogen. Recent outbreaks in Venezuela and Colombia in 1995, involving an estimated 100,000 human cases, indicate that VEEV still poses a serious public health threat. To develop a safe, efficient vaccine that protects against disease resulting from VEEV infection, we generated chimeric Sindbis (SIN) viruses expressing structural proteins of different strains of VEEV and analyzed their replication in vitro and in vivo, as well as the characteristics of the induced immune responses. None of the chimeric SIN/VEE viruses caused any detectable disease in adult mice after either intracerebral (i.c.) or subcutaneous (s.c.) inoculation, and all chimeras were more attenuated than the vaccine strain, VEEV TC83, in 6-day-old mice after i.c. infection. All vaccinated mice were protected against lethal encephalitis following i.c., s.c., or intranasal (i.n.) challenge with the virulent VEEV ZPC738 strain (ZPC738). In spite of the absence of clinical encephalitis in vaccinated mice challenged with ZPC738 via i.n. or i.c. route, we regularly detected high levels of infectious challenge virus in the central nervous system (CNS). However, infectious virus was undetectable in the brains of all immunized animals at 28 days after challenge. Hamsters vaccinated with chimeric SIN/VEE viruses were also protected against s.c. challenge with ZPC738. Taken together, our findings suggest that these chimeric SIN/VEE viruses are safe and efficacious in adult mice and hamsters and are potentially useful as VEEV vaccines. In addition, immunized animals provide a useful model for studying the mechanisms of the anti-VEEV neuroinflammatory response, leading to the reduction of viral titers in the CNS and survival of animals.

scholarly journals Role of Dendritic Cell Targeting in Venezuelan Equine Encephalitis Virus Pathogenesis

2000 ◽  
Vol 74 (2) ◽  
pp. 914-922 ◽  
Author(s):  
Gene H. MacDonald ◽  
Robert E. Johnston
Keyword(s):  
Dendritic Cells ◽  
Lymph Node ◽  
Venezuelan Equine Encephalitis Virus ◽  
Encephalitis Virus ◽  
Lymphoid Tissues ◽  
Venezuelan Equine Encephalitis ◽  
Equine Encephalitis Virus ◽  
Viral Spread ◽  
Draining Lymph Node

ABSTRACT The initial steps of Venezuelan equine encephalitis virus (VEE) spread from inoculation in the skin to the draining lymph node have been characterized. By using green fluorescent protein and immunocytochemistry, dendritic cells in the draining lymph node were determined to be the primary target of VEE infection in the first 48 h following inoculation. VEE viral replicon particles, which can undergo only one round of infection, identified Langerhans cells to be the initial set of cells infected by VEE directly following inoculation. These cells are resident dendritic cells in the skin, which migrate to the draining lymph node following activation. A point mutation in the E2 glycoprotein gene of VEE that renders the virus avirulent and compromises its ability to spread beyond the draining lymph blocked the appearance of virally infected dendritic cells in the lymph node in vivo. A second-site suppressor mutation that restores viral spread to lymphoid tissues and partially restore virulence likewise restored the ability of VEE to infect dendritic cells in vivo.

scholarly journals Acute Infection with Venezuelan Equine Encephalitis Virus Replicon Particles Catalyzes a Systemic Antiviral State and Protects from Lethal Virus Challenge

2009 ◽  
Vol 83 (23) ◽  
pp. 12432-12442 ◽  
Author(s):  
Jennifer L. Konopka ◽  
Joseph M. Thompson ◽  
Alan C. Whitmore ◽  
Drue L. Webb ◽  
Robert E. Johnston
Keyword(s):  
Acute Infection ◽  
Venezuelan Equine Encephalitis Virus ◽  
Encephalitis Virus ◽  
Venezuelan Equine Encephalitis ◽  
Innate Response ◽  
Lethal Challenge ◽  
Antiviral State ◽  
Equine Encephalitis Virus ◽  
Pathogen Invasion

ABSTRACT The host innate immune response provides a critical first line of defense against invading pathogens, inducing an antiviral state to impede the spread of infection. While numerous studies have documented antiviral responses within actively infected tissues, few have described the earliest innate response induced systemically by infection. Here, utilizing Venezuelan equine encephalitis virus (VEE) replicon particles (VRP) to limit infection to the initially infected cells in vivo, a rapid activation of the antiviral response was demonstrated not only within the murine draining lymph node, where replication was confined, but also within distal tissues. In the liver and brain, expression of interferon-stimulated genes was detected by 1 to 3 h following VRP footpad inoculation, reaching peak expression of >100-fold over that in mock-infected animals. Moreover, mice receiving a VRP footpad inoculation 6, 12, or 24 h prior to an otherwise lethal VEE footpad challenge were completely protected from death, including a drastic reduction in challenge virus titers. VRP pretreatment also provided protection from intranasal VEE challenge and extended the average survival time following intracranial challenge. Signaling through the interferon receptor was necessary for antiviral gene induction and protection from VEE challenge. However, VRP pretreatment failed to protect mice from a heterologous, lethal challenge with vesicular stomatitis virus, yet conferred protection following challenge with influenza virus. Collectively, these results document a rapid modulation of the host innate response within hours of infection, capable of rapidly alerting the entire animal to pathogen invasion and leading to protection from viral disease.

scholarly journals Resveratrol Inhibits Venezuelan Equine Encephalitis Virus Infection by Interfering with the AKT/GSK Pathway

Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 346
Author(s):  
Caitlin W. Lehman ◽  
Kylene Kehn-Hall ◽  
Megha Aggarwal ◽  
Nicole R. Bracci ◽  
Han-Chi Pan ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Fluorescent Protein ◽  
Glycogen Synthase ◽  
Venezuelan Equine Encephalitis Virus ◽  
Encephalitis Virus ◽  
Host Cells ◽  
Dynamics Simulation ◽  
Luciferase Reporter ◽  
Venezuelan Equine Encephalitis ◽  
Equine Encephalitis Virus

The host proteins Protein Kinase B (AKT) and glycogen synthase kinase-3 (GSK-3) are associated with multiple neurodegenerative disorders. They are also important for the replication of Venezuelan equine encephalitis virus (VEEV), thereby making the AKT/GSK-3 pathway an attractive target for developing anti-VEEV therapeutics. Resveratrol, a natural phytochemical, has been shown to substantially inhibit the AKT pathway. Therefore, we attempted to explore whether it exerts any antiviral activity against VEEV. In this study, we utilized green fluorescent protein (GFP)- and luciferase-encoding recombinant VEEV to determine the cytotoxicity and antiviral efficacy via luciferase reporter assays, flow cytometry, and immunofluorescent assays. Our results indicate that resveratrol treatment is capable of inhibiting VEEV replication, resulting in increased viability of Vero and U87MG cells as well as reduced virion production and viral RNA contents within host cells for at least 48 h with a single treatment. Furthermore, the suppression of apoptotic signaling adaptors, caspase-3, caspase-7, and annexin V may also be implicated in resveratrol-mediated antiviral activity. We found that decreased phosphorylation of the AKT/GSK-3 pathway, mediated by resveratrol, can be triggered during the early stages of VEEV infection, suggesting that resveratrol disrupts the viral replication cycle and consequently promotes cell survival. Finally, molecular docking and dynamics simulation studies revealed that resveratrol can directly bind to VEEV glycoproteins, which may interfere with virus attachment and entry. In conclusion, our results suggest that resveratrol exerts inhibitory activity against VEEV infection and upon further modification could be a useful compound to study in neuroprotective research and veterinary sciences.

scholarly journals Spatial Dispersion of Adult Mosquitoes (Diptera: Culicidae) in a Sylvatic Focus of Venezuelan Equine Encephalitis Virus

2001 ◽  
Vol 38 (6) ◽  
pp. 813-821 ◽  
Author(s):  
Wilmer Méndez ◽  
Jonathan Liria ◽  
Juan-Carlos Navarro ◽  
Carmen Z. García ◽  
Jerome E. Freier ◽  
...  
Keyword(s):  
Spatial Dispersion ◽  
Venezuelan Equine Encephalitis Virus ◽  
Encephalitis Virus ◽  
Venezuelan Equine Encephalitis ◽  
Equine Encephalitis Virus

Congenital cerebral and ocular malformations induced in rhesus monkeys by Venezuelan Equine Encephalitis virus

Teratology ◽  
1977 ◽  
Vol 16 (3) ◽  
pp. 285-295 ◽  
Author(s):  
W. T. London ◽  
Neil H. Levitt ◽  
Stephen G. Kent ◽  
Vernon G. Wong ◽  
John L. Sever
Keyword(s):  
Rhesus Monkeys ◽  
Venezuelan Equine Encephalitis Virus ◽  
Encephalitis Virus ◽  
Venezuelan Equine Encephalitis ◽  
Equine Encephalitis Virus
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