scholarly journals Pegylated Alpha Interferon Is an Effective Treatment for Virulent Venezuelan Equine Encephalitis Virus and Has Profound Effects on the Host Immune Response to Infection

2000 ◽  
Vol 74 (11) ◽  
pp. 5006-5015 ◽  
Author(s):  
Roman A. Lukaszewski ◽  
Timothy J. G. Brooks
Keyword(s):  
Immune Response ◽  
Prolonged Exposure ◽  
Venezuelan Equine Encephalitis Virus ◽  
Encephalitis Virus ◽  
Alpha Interferon ◽  
Small Rodent ◽  
Lymphoid Tissues ◽  
Venezuelan Equine Encephalitis ◽  
Equine Encephalitis Virus ◽  
Immunological Mechanisms

ABSTRACT Venezuelan equine encephalitis virus (VEEV) is a highly infectious alphavirus endemic in parts of Central and South America. The disease is transmitted by mosquitoes, and the natural reservoir is the small rodent population, with epidemics occurring in horses and occasionally humans. Following infection, VEEV replicates in lymphoid tissues prior to invasion of the central nervous system. Treatment of VEEV-infected BALB/c mice with polyethylene glycol-conjugated alpha interferon (PEG IFN-α) results in a greatly enhanced survival from either a subcutaneous or an aerosol infection. Virus is undetectable within PEG IFN-α-treated individuals by day 30 postinfection (p.i.). Treatment results in a number of changes to the immune response characteristics normally associated with VEEV infection. Increased macrophage activation occurs in PEG IFN-α-treated BALB/c mice infected with VEEV. The rapid activation of splenic CD4, CD8, and B cells by day 2 p.i. normally associated with VEEV infection is absent in PEG IFN-α-treated mice. The high tumor necrosis factor alpha production by macrophages from untreated mice is greatly diminished in PEG IFN-α-treated mice. These results suggest key immunological mechanisms targeted by this lethal alphavirus that can be modulated by prolonged exposure to IFN-α.

Murine T-helper cell immune response to recombinant vaccinia—Venezuelan equine encephalitis virus

Vaccine ◽  
1994 ◽  
Vol 12 (7) ◽  
pp. 620-624 ◽  
Author(s):  
James H. Mathews ◽  
Richard M. Kinney ◽  
John T. Roehrig ◽  
Alan D.T. Barrett ◽  
Dennis W. Trent
Keyword(s):  
Immune Response ◽  
Venezuelan Equine Encephalitis Virus ◽  
Encephalitis Virus ◽  
T Helper Cell ◽  
Helper Cell ◽  
Cell Immune Response ◽  
Venezuelan Equine Encephalitis ◽  
T Helper ◽  
Recombinant Vaccinia ◽  
Equine Encephalitis Virus

scholarly journals Alpha interferon as an adenovirus-vectored vaccine adjuvant and antiviral in Venezuelan equine encephalitis virus infection

2009 ◽  
Vol 90 (4) ◽  
pp. 874-882 ◽  
Author(s):  
Lyn O'Brien ◽  
Stuart Perkins ◽  
Amanda Williams ◽  
Lin Eastaugh ◽  
Amanda Phelps ◽  
...  
Keyword(s):  
Virus Infection ◽  
Adenovirus Vector ◽  
Venezuelan Equine Encephalitis Virus ◽  
Encephalitis Virus ◽  
Alpha Interferon ◽  
Specific Response ◽  
Venezuelan Equine Encephalitis ◽  
Direct Role ◽  
Equine Encephalitis Virus ◽  
Vectored Vaccine

There are no widely available vaccines or antiviral drugs capable of protecting against infection with Venezuelan equine encephalitis virus (VEEV), although an adenovirus vector expressing VEEV structural proteins protects mice from challenge with VEEV and is potentially a vaccine suitable for human use. This work examines whether alpha interferon (IFN-α) could act as an adjuvant for the adenovirus-based vaccine. IFN-α was either expressed by a plasmid linked to the adenovirus vaccine or encoded by a separate adenovirus vector administered as a mixture with the vaccine. In contrast to previous reports with other vaccines, the presence of IFN-α reduced the antibody response to VEEV. When IFN-α was encoded by adenovirus, the lack of a VEEV-specific response was accompanied by an increase in the immune response to the adenovirus vector. IFN-α also plays a direct role in defence against virus infection, inducing the expression of a large number of antiviral proteins. Adenovirus-delivered IFN-α protected mice from VEEV disease when administered 24 h prior to challenge, but not when administered 6 h post-challenge, suggesting that up to 24 h is required for the development of the IFN-mediated antiviral response.

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 Replicon Particles of Venezuelan Equine Encephalitis Virus as a Reductionist Murine Model for Encephalitis

2009 ◽  
Vol 83 (9) ◽  
pp. 4275-4286 ◽  
Author(s):  
Alexandra Schäfer ◽  
Alan C. Whitmore ◽  
Jennifer L. Konopka ◽  
Robert E. Johnston
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Adaptive Immune Response ◽  
Venezuelan Equine Encephalitis Virus ◽  
Encephalitis Virus ◽  
Innate Immune ◽  
Venezuelan Equine Encephalitis ◽  
Equine Encephalitis Virus ◽  
Adaptive Immune ◽  
Inflammatory Monocytes

ABSTRACT Venezuelan equine encephalitis virus (VEE) replicon particles (VRP) were used to model the initial phase of VEE-induced encephalitis in the mouse brain. VRP can target and infect cells as VEE, but VRP do not propagate beyond the first infected cell due to the absence of the structural genes. Direct intracranial inoculation of VRP into mice induced acute encephalitis with signs similar to the neuronal phase of wild-type VEE infection and other models of virus-induced encephalitis. Using the previously established VRP-mRNP tagging system, a new method to distinguish the host responses in infected cells from those in uninfected bystander cell populations, we detected a robust and rapid innate immune response in the central nervous system (CNS) by infected neurons and uninfected bystander cells. Moreover, this innate immune response in the CNS compromised blood-brain barrier integrity, created an inflammatory response, and directed an adaptive immune response characterized by proliferation and activation of microglia cells and infiltration of inflammatory monocytes, in addition to CD4+ and CD8+ T lymphocytes. Taken together, these data suggest that a naïve CNS has an intrinsic potential to induce an innate immune response that could be crucial to the outcome of the infection by determining the composition and dynamics of the adaptive immune response. Furthermore, these results establish a model for neurotropic virus infection to identify host and viral factors that contribute to invasion of the brain, the mechanism(s) whereby the adaptive immune response can clear the infection, and the role of the host innate response in these processes.

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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