Monoclonal antibody cure and prophylaxis of lethal Sindbis virus encephalitis in mice

Stanley, J. L.; Cooper, Stephen R.; Griffin, Diane E.

doi:10.1128/jvi.58.1.107-115.1986

Cited by 59 publications

(29 citation statements)

References 35 publications

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“…The B cells producing these antibodies are first detected in the spleens of infected animals before appearing in the brain (Tyor and Griffin, 1993), although their need to physically traverse the BBB in order for antibodies to reach foci of infection is debatable. Indeed, prior studies have shown that the intravenous transfer of immune serum or monoclonal anti-viral antibodies is sufficient to promote viral clearance and recovery in SV-infected mice, provided that enough material is given (Stanley et al, 1986;Levine et al, 1991). In this disease setting, the influx of B cells into the CNS may be more important to establish a local population of anti-viral effectors that are retained at that site well after viral clearance has been achieved in order to prevent late viral recrudescence (Tyor et al, 1992;Griffin et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

The lymphoid chemokine, CXCL13, is dispensable for the initial recruitment of B cells to the acutely inflamed central nervous system

Rainey-Barger

Rumble

Lalor

et al. 2011

Brain, Behavior, and Immunity

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Cases of progressive multifocal leukoencephalopathy can occur in patients treated with the B cell depleting anti-CD20 antibody, rituximab, highlighting the importance of B cell surveillance of the central nervous system (CNS). The lymphoid chemokine, CXCL13, is critical for B cell recruitment and functional organization of peripheral lymphoid tissues, and CXCL13 levels are often elevated in the inflamed CNS. To more directly investigate the role of CXCL13 in CNS B cell migration, its role in animal models of infectious and inflammatory demyelinating disease was examined. During acute alphavirus encephalitis where viral clearance depends on the local actions of anti-viral antibodies, CXCL13 levels and B cell numbers increased in brain tissue over time. Surprisingly, however, CXCL13-deficient animals showed normal CNS B cell recruitment, unaltered CNS virus replication and clearance, and intact peripheral anti-viral antibody responses. During experimental autoimmune encephalomyelitis (EAE), CNS levels of CXCL13 increased as symptoms emerged and equivalent numbers of B cells were identified among the CNS infiltrates of CXCL13-deficient mice compared to control animals. However, CXCL13-deficient mice did not sustain pathogenic anti-myelin T cell responses, consistent with their known propensity to develop more self-limited EAE. These data show that CXCL13 is dispensable for CNS B cell recruitment in both models. The disease course is unaffected by CXCL13 in a CNS infection paradigm that depends on a pathogen-specific B cell response, while it is heightened and prolonged by CXCL13 when myelin-specific CD4+ T cells drive CNS pathology. Thus, CXCL13 could be a therapeutic target in certain neuroinflammatory diseases, but not by blocking B cell recruitment to the CNS.

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Section: Discussionmentioning

confidence: 99%

The lymphoid chemokine, CXCL13, is dispensable for the initial recruitment of B cells to the acutely inflamed central nervous system

Rainey-Barger

Rumble

Lalor

et al. 2011

Brain, Behavior, and Immunity

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“…The method for measuring complement-mediated lysis of infected cells was a modification of a protocol to quantitate complement-mediated lysis of Sindbis virus-infected cells (61). Briefly, MC57GL cells were infected at a multiplicity of infection (MOI) of 5 or mock infected.…”

Section: Methodsmentioning

confidence: 99%

Complement Activation Is Required for Induction of a Protective Antibody Response against West Nile Virus Infection

Mehlhop

Whitby²,

Oliphant

et al. 2005

J Virol

146

134

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Infection with West Nile virus (WNV) causes a severe infection of the central nervous system (CNS) with higher levels of morbidity and mortality in the elderly and the immunocompromised. Experiments with mice have begun to define how the innate and adaptive immune responses function to limit infection. Here, we demonstrate that the complement system, a major component of innate immunity, controls WNV infection in vitro primarily in an antibody-dependent manner by neutralizing virus particles in solution and lysing WNV-infected cells. More decisively, mice that genetically lack the third component of complement or complement receptor 1 (CR1) and CR2 developed increased CNS virus burdens and were vulnerable to lethal infection at a low dose of WNV. Both C3-deficient and CR1-and CR2-deficient mice also had significant deficits in their humoral responses after infection with markedly reduced levels of specific anti-WNV immunoglobulin M (IgM) and IgG. Overall, these results suggest that complement controls WNV infection, in part through its ability to induce a protective antibody response.

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“…In more recent experiments using an otherwise lethal strain of Sindbis virus, animals preimmunized against nonstructural viral proteins were highly protected against permanent paralysis and death (Gorrell et al, 1997). This protection was not associated with either reduced virus replication in the brain or altered virus tropism (neurons of the brain and spinal cord remained the principal target of infection), nor was it due to an augmented humoral response against structural viral proteins that could also protect lethally infected animals (Stanley et al, 1986;Gorrell et al, 1997). Instead, this nonstructural proteinmediated protection proved to be a function of immune T cells and occurred by promoting the survival and functional recovery of virus-infected neurons (Gorrell et al, 1997).…”

Section: T Cells Can Protect Hosts From Lethal Cns Viral Infectionmentioning

confidence: 98%

Regulation of t cell responses during central nervous system viral infection

Irani

Griffin

2001

Advances in Virus Research

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Monoclonal antibody cure and prophylaxis of lethal Sindbis virus encephalitis in mice

Cited by 59 publications

References 35 publications

The lymphoid chemokine, CXCL13, is dispensable for the initial recruitment of B cells to the acutely inflamed central nervous system

The lymphoid chemokine, CXCL13, is dispensable for the initial recruitment of B cells to the acutely inflamed central nervous system

Complement Activation Is Required for Induction of a Protective Antibody Response against West Nile Virus Infection

Regulation of t cell responses during central nervous system viral infection

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