Innate and Adaptive Immune Responses Determine Protection against Disseminated Infection by West Nile Encephalitis Virus

Diamond, Michael S.; Shrestha, Bimmi; Mehlhop, Erin; Sitati, Elizabeth; Engle, Michael J.

doi:10.1089/088282403322396082

Cited by 183 publications

(160 citation statements)

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“…PRR signaling leads to the induction of adaptive immune responses, which are required for clearance of viral infections in the CNS [220][221][222]. Increased permeability of the BBB following arboviral infection allows entry of B cells and neutralizing Abs (nAbs) into the CNS.…”

Section: Viral Clearance From the Cnsmentioning

confidence: 99%

“…Once in the CNS, nAbs bind cell-free viruses, preventing new viral infections. Mice deficient for B cells and antibody production demonstrated higher viral loads in CNS and increased vulnerability to lethal WNV infection than wild-type mice [221]. Similarly, adoptive transfer of monoclonal antibodies protected mice from lethal encephalitis caused by other flaviviruses, namely JEV [223], SLEV [224], and yellow fever virus [225].…”

Section: Viral Clearance From the Cnsmentioning

confidence: 99%

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Encephalitic Arboviruses: Emergence, Clinical Presentation, and Neuropathogenesis

2016

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Arboviruses are arthropod-borne viruses that exhibit worldwide distribution, contributing to systemic and neurologic infections in a variety of geographical locations. Arboviruses are transmitted to vertebral hosts during blood feedings by mosquitoes, ticks, biting flies, mites, and nits. While the majority of arboviral infections do not lead to neuroinvasive forms of disease, they are among the most severe infectious risks to the health of the human central nervous system. The neurologic diseases caused by arboviruses include meningitis, encephalitis, myelitis, encephalomyelitis, neuritis, and myositis in which virus-and immune-mediated injury may lead to severe, persisting neurologic deficits or death. Here we will review the major families of emerging arboviruses that cause neurologic infections, their neuropathogenesis and host neuroimmunologic responses, and current strategies for treatment and prevention of neurologic infections they cause.

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Section: Viral Clearance From the Cnsmentioning

confidence: 99%

Section: Viral Clearance From the Cnsmentioning

confidence: 99%

Encephalitic Arboviruses: Emergence, Clinical Presentation, and Neuropathogenesis

2016

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“…The humoral immune response is crucial for protection against flavivirus infection and disease (19). Antibodies can prevent infection by interference with functions mediated by viral surface proteins, such as receptor attachment, virus internalization, and membrane fusion.…”

Section: W Est Nile Virus (Wnv) Causes a Febrile Illness In Humansmentioning

confidence: 99%

West Nile virus in complex with the Fab fragment of a neutralizing monoclonal antibody

Kaufmann

Nybakken

Chipman

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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120

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Flaviviruses, such as West Nile virus (WNV), are significant human pathogens. The humoral immune response plays an important role in the control of flavivirus infection and disease. The structure of WNV complexed with the Fab fragment of the strongly neutralizing mAb E16 was determined to 14.5-Å resolution with cryoelectron microscopy. E16, an antibody with therapeutic potential, binds to domain III of the WNV envelope glycoprotein. Because of steric hindrance, Fab E16 binds to only 120 of the 180 possible binding sites on the viral surface. Fitting of the previously determined x-ray structure of the Fab-domain III complex into the cryo-electron microscopy density required a change of the elbow angle between the variable and constant domains of the Fab. The structure suggests that the E16 antibody neutralizes WNV by blocking the initial rearrangement of the E glycoprotein before fusion with a cellular membrane.cryo-electron microscopy ͉ flavivirus ͉ neutralization W est Nile virus (WNV) causes a febrile illness in humans that can progress to encephalitis, paralysis, and death. Although endemic in parts of Africa, Asia, Europe, and the Middle East, it was first isolated in the United States in 1999 and has subsequently spread throughout North America and the Caribbean (1-3). The similar Kunjin virus is found in Australia (4). WNV, a member of the Flaviviridae family, is closely related to other arthropod-borne, medically important viruses, such as dengue, yellow fever, Japanese encephalitis, and tick-borne encephalitis viruses. These small, Ϸ500-Å-diameter, lipidenveloped viruses enter their host cells by receptor-mediated endocytosis. A low pH-triggered conformational rearrangement of the viral surface glycoproteins resulting in a fusion-active state of the virion allows the release of the single-stranded, positivesense RNA genome from the endosomes into the cytoplasm.The outer surface of mature infectious particles is formed by an icosahedral scaffold of 90 homodimers of the membraneanchored envelope glycoprotein (E). The three E monomers per icosahedral asymmetric unit each have distinctly different environments (5, 6), contrary to most other icosahedral viruses in which all subunits have at least quasi-similar environments. The ectodomain of E consists of three structural domains, DI, DII, and DIII (7-9). DI is structurally positioned between DII and DIII. The dimerization DII contains a 12-residue-long loop essential for virus-cell membrane fusion and, in dengue virus, has carbohydrate moieties that mediate receptor binding (10). The C-terminal DIII undergoes a major, pH-triggered, positional rearrangement essential for fusion and may also be involved in receptor binding (7,(11)(12)(13)(14)(15)(16)(17)(18).The humoral immune response is crucial for protection against flavivirus infection and disease (19). Antibodies can prevent infection by interference with functions mediated by viral surface proteins, such as receptor attachment, virus internalization, and membrane fusion. Indeed, the E glycoprotein is the...

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“…In mice, IFN-/ , B cells and antibody, complement, and CD8 + T cells, all have crucial roles in the control of WNV infection. 23,[41][42][43][44] In addition, secretion by WNV-infected neurons of the chemokine CXCL10 facilitates recruitment of CD8 + T cells to the CNS. 45,46 WNV infection leads to activation of Tlr3, which recognizes viral double-stranded RNA.…”

Section: Risk Factorsmentioning

confidence: 99%

“…60 IFN-2b inhibits growth of WNV in vitro and can protect BALB/c mice and golden hamsters from WNV-induced disease, although its efficacy is greatly diminished when treatments are delayed beyond 4-6 hours before viral challenge. 41,44,58 IFN-/ -receptor knockout mice have increased mortality following WNV challenge, whereas treatment of primary mouse neuronal cultures with IFN-before or after infection increased neuronal survival in dependently of the effect on WNV replication. 44 The efficacy of IFN treatment in humans is still unclear, as it has only been studied in a non-blinded, non-placebocontrolled clinical trial.…”

Section: Current Treatment and Prospects For Future Therapies Therapementioning

confidence: 99%

West Nile virus meningoencephalitis

2006

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SUMMARYSince its first appearance in the US in 1999, West Nile virus (WNV) has emerged as the most common cause of epidemic meningoencephalitis in North America. In the 6 years following the 1999 outbreak, the geographic range and burden of the disease in birds, mosquitoes and humans has greatly expanded to include the 48 contiguous US and 7 Canadian provinces, as well as Mexico, the Caribbean islands and Colombia. WNV has shown an increasing propensity for neuroinvasive disease over the past decade, with varied presentations including meningitis, encephalitis and acute flaccid paralysis. Although neuroinvasive disease occurs in less than 1% of infected individuals, it is associated with high mortality. From 1999-2005, more than 8,000 cases of neuroinvasive WNV disease were reported in the US, resulting in over 780 deaths. In this review, we discuss epidemiology, risk factors, clinical features, diagnosis and prognosis of WNV meningoencephalitis, along with potential treatments.

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Innate and Adaptive Immune Responses Determine Protection against Disseminated Infection by West Nile Encephalitis Virus

Cited by 183 publications

References 168 publications

Encephalitic Arboviruses: Emergence, Clinical Presentation, and Neuropathogenesis

Encephalitic Arboviruses: Emergence, Clinical Presentation, and Neuropathogenesis

West Nile virus in complex with the Fab fragment of a neutralizing monoclonal antibody

West Nile virus meningoencephalitis

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