West Nile Virus spread and differential chemokine response in the central nervous system of mice: Role in pathogenic mechanisms of encephalitis

2019 ◽  
Vol 67 (2) ◽  
pp. 799-810 ◽  
Author(s):  
Beatriz Vidaña ◽  
Nicholas Johnson ◽  
Anthony R. Fooks ◽  
Pedro J. Sánchez‐Cordón ◽  
Daniel J. Hicks ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
West Nile Virus ◽  
Virus Spread ◽  
West Nile ◽  
Pathogenic Mechanisms ◽  
The Central Nervous System

scholarly journals West Nile Virus Infection in the Central Nervous System

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 105 ◽  
Author(s):  
Evandro R. Winkelmann ◽  
Huanle Luo ◽  
Tian Wang
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
West Nile Virus ◽  
Animal Models ◽  
West Nile Virus Infection ◽  
The United States ◽  
West Nile ◽  
Neurological Sequelae ◽  
The Central Nervous System

West Nile virus (WNV), a neurotropic single-stranded flavivirus has been the leading cause of arboviral encephalitis worldwide.  Up to 50% of WNV convalescent patients in the United States were reported to have long-term neurological sequelae.  Neither antiviral drugs nor vaccines are available for humans.  Animal models have been used to investigate WNV pathogenesis and host immune response in humans.  In this review, we will discuss recent findings from studies in animal models of WNV infection, and provide new insights on WNV pathogenesis and WNV-induced host immunity in the central nervous system.

scholarly journals The Role of Microglia during West Nile Virus Infection of the Central Nervous System

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 485 ◽  
Author(s):  
Sarah Stonedahl ◽  
Penny Clarke ◽  
Kenneth L. Tyler
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
West Nile Virus ◽  
Immune Cells ◽  
Neuronal Cell ◽  
The United States ◽  
Health Concern ◽  
West Nile ◽  
The Central Nervous System

Encephalitis resulting from viral infections is a major cause of hospitalization and death worldwide. West Nile Virus (WNV) is a substantial health concern as it is one of the leading causes of viral encephalitis in the United States today. WNV infiltrates the central nervous system (CNS), where it directly infects neurons and induces neuronal cell death, in part, via activation of caspase 3-mediated apoptosis. WNV infection also induces neuroinflammation characterized by activation of innate immune cells, including microglia and astrocytes, production of inflammatory cytokines, breakdown of the blood-brain barrier, and infiltration of peripheral leukocytes. Microglia are the resident immune cells of the brain and monitor the CNS for signs of injury or pathogens. Following infection with WNV, microglia exhibit a change in morphology consistent with activation and are associated with increased expression of proinflammatory cytokines. Recent research has focused on deciphering the role of microglia during WNV encephalitis. Microglia play a protective role during infections by limiting viral growth and reducing mortality in mice. However, it also appears that activated microglia are triggered by T cells to mediate synaptic elimination at late times during infection, which may contribute to long-term neurological deficits following a neuroinvasive WNV infection. This review will discuss the important role of microglia in the pathogenesis of a neuroinvasive WNV infection. Knowledge of the precise role of microglia during a WNV infection may lead to a greater ability to treat and manage WNV encephalitis.

scholarly journals The Innate Immune Adaptor Molecule MyD88 Restricts West Nile Virus Replication and Spread in Neurons of the Central Nervous System

2010 ◽  
Vol 84 (23) ◽  
pp. 12125-12138 ◽  
Author(s):  
Kristy J. Szretter ◽  
Stephane Daffis ◽  
Jigisha Patel ◽  
Mehul S. Suthar ◽  
Robyn S. Klein ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
West Nile Virus ◽  
Virus Replication ◽  
Independent Effect ◽  
Type I ◽  
Rna Helicases ◽  
West Nile ◽  
The Central Nervous System ◽  
The Brain

ABSTRACT Type I interferons (IFN-α/β) control viral infection by triggering the expression of genes that restrict transcription, translation, replication, and assembly. Many viruses induce IFN responses after recognition by cytoplasmic or endosomal RNA sensors (RIG-I-like RNA helicases [RLR] and Toll-like receptors [TLR]), which signal through the cognate adaptor signaling molecules IPS-1, TRIF, and MyD88. Recent studies have demonstrated that IPS-1-dependent induction of IFN-α/β downstream of RLR recognition restricts West Nile virus (WNV) infection in many cell types, whereas TRIF-dependent TLR3 signaling limits WNV replication in neurons. Here, we examined the contribution of MyD88 signaling to the control of WNV by evaluating IFN induction and virus replication in genetically deficient cells and mice. MyD88 − / − mice showed increased lethality after WNV infection and elevated viral burden primarily in the brain, even though little effect on the systemic type I IFN response was observed. Intracranial inoculation studies corroborated these findings, as WNV spread more rapidly in the central nervous system of MyD88 − / − mice, and this phenotype preceded the recruitment of inflammatory leukocytes. In vitro, increased WNV replication was observed in MyD88 − / − macrophages and subsets of neurons but not in myeloid dendritic cells. MyD88 had an independent effect on recruitment of monocyte-derived macrophages and T cells into the brain that was associated with blunted induction of the chemokines that attract leukocytes. Our experiments suggest that MyD88 restricts WNV by inhibiting replication in subsets of cells and modulating expression of chemokines that regulate immune cell migration into the central nervous system.

scholarly journals A Critical Role for Induced IgM in the Protection against West Nile Virus Infection

2003 ◽  
Vol 198 (12) ◽  
pp. 1853-1862 ◽  
Author(s):  
Michael S. Diamond ◽  
Elizabeth M. Sitati ◽  
Lindzy D. Friend ◽  
Stephen Higgs ◽  
Bimmi Shrestha ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
West Nile Virus ◽  
Critical Role ◽  
West Nile Virus Infection ◽  
The Elderly ◽  
Wild Type ◽  
West Nile ◽  
Lethal Infection ◽  
The Central Nervous System

In humans, the elderly and immunocompromised are at greatest risk for disseminated West Nile virus (WNV) infection, yet the immunologic basis for this remains unclear. We demonstrated previously that B cells and IgG contributed to the defense against disseminated WNV infection (Diamond, M.S., B. Shrestha, A. Marri, D. Mahan, and M. Engle. 2003. J. Virol. 77:2578–2586). In this paper, we addressed the function of IgM in controlling WNV infection. C57BL/6J mice (sIgM−/−) that were deficient in the production of secreted IgM but capable of expressing surface IgM and secreting other immunoglobulin isotypes were vulnerable to lethal infection, even after inoculation with low doses of WNV. Within 96 h, markedly higher levels of infectious virus were detected in the serum of sIgM−/− mice compared with wild-type mice. The enhanced viremia correlated with higher WNV burdens in the central nervous system, and was also associated with a blunted anti-WNV IgG response. Passive transfer of polyclonal anti-WNV IgM or IgG protected sIgM−/− mice against mortality, although administration of comparable amounts of a nonneutralizing monoclonal anti-WNV IgM provided no protection. In a prospective analysis, a low titer of anti-WNV IgM antibodies at day 4 uniformly predicted mortality in wild-type mice. Thus, the induction of a specific, neutralizing IgM response early in the course of WNV infection limits viremia and dissemination into the central nervous system, and protects against lethal infection.

Sign in / Sign up

Export Citation Format

Share Document