Pathogenesis of encephalitis induced in newborn mice by virulent and avirulent strains of Sindbis virus

Sherman, Linda A.; Griffin, Diane E.

doi:10.1128/jvi.64.5.2041-2046.1990

Cited by 47 publications

(24 citation statements)

References 29 publications

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“…2 A, middle). The extensive neuronal death was consistent with the known tropism of SINV to replicate mainly in the neurons of the CNS (Jackson et al, 1987Sherman and Griffin, 1990). Next, we looked for accumulation of lymphocytes and plasma cells around blood vessels, which was minimal in the brains of both SVN-infected WT and moribund Irf2 −/− mice ( Fig.…”

Section: Massive Neuronal Death In Irf2 −/− Mouse Brains Is Not Accomsupporting

confidence: 82%

Interferon regulatory factor 2 protects mice from lethal viral neuroinvasion

Bozzacco

Hoffmann

et al. 2016

Journal of Experimental Medicine

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Section: Massive Neuronal Death In Irf2 −/− Mouse Brains Is Not Accomsupporting

confidence: 82%

Interferon regulatory factor 2 protects mice from lethal viral neuroinvasion

Bozzacco

Hoffmann

et al. 2016

Journal of Experimental Medicine

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“…This may be related to the maintenance of Na+K+ATPase activity by MAb cross-linking of E2 at the plasma membrane since integrity of the Na* pump has been postulated to be critical for the transcriptional activation of interferon-.stimulated regulatory elements (41). Interferon and antibody to SV are both produced locally in thtbrains of infected mice (6,10,23,(42)(43)(44). We hypothesize that interferons act synergistically with antibody to control SV replication in vivo, as has been suggested for other viruses (45)(46)(47),…”

Section: Is Antibody Sufficient To Completely Suppress Intracellular mentioning

confidence: 99%

The role of antibody in recovery from alphavirus encephalitis

Griffin

Levine²,

Tyor

et al. 1997

Immunological Reviews

112

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Alphaviruses infect neurons in the brain and spinal cord and cause acute encephalomyelitis in a variety of mammals. The outcome of infection is determined by whether the neurons survive infection and this, in turn, is determined by the virulence of the virus and the age of the host at the time of infection. We have been studying Sindbis virus (SV) infection of mice as a model system for alphavirus-induced encephalomyelitis. Investigation of intracerebral infection of weanling mice with two different strains of SV has allowed us to analyze the role of the immune response in protection from fatal disease (virulent NSV strain) and in clearance of virus from the nervous system during non-fatal disease (less virulent SV AR339 strain). Neutralizing and non-neutralizing antibodies to the E1 and E2 surface glycoproteins can protect mice from fatal NSV infection when given before or after infection, while T cells are not protective. The mechanism of antibody-mediated protection is not known, but it is likely that more than one mechanism is involved and that different mechanisms are involved in pre-infection and post-infection treatment protection. Clearance of infectious virus from the nervous system of mice during recovery from non-fatal disease is accomplished by antibodies to the E2 glycoprotein. The process does not involve damage to the infected neurons and is independent of complement and mononuclear cells. Bivalent antibody is required and binds to the surface of the infected cell. Initially, release of virus by budding from the cell surface is prevented and, subsequently, intracellular virus replication is inhibited possibly through antiviral mechanisms induced in co-operation with interferon. This non-lytic mechanism for control of virus infection results in the prolonged presence of viral RNA in tissue and the need for prolonged intrathecal synthesis of antiviral antibody by B cells within the central nervous system.

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“…To address these questions, we used an experimental model of wild-type SV infection in adult BALB/c and scid/CB17 mice. SV is a single-stranded positive-strand RNA virus that replicates predominantly in neurons after intracerebral inoculation in adult mice (14,15,29). As previously described (19), immunocompetent mice develop clinically silent, self-limiting encephalitis in which infectious virus is cleared within 8 days after infection.…”

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confidence: 99%

Persistence of viral RNA in mouse brains after recovery from acute alphavirus encephalitis

Griffin

1992

J Virol

Self Cite

110

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Little is known about the relationship between recovery from acute viral encephalitis and the clearance of viral genetic material from the central nervous system. In a mouse model of Sindbis virus encephalitis, we have previously shown that clearance of infectious virus is mediated by antibody-induced restriction of viral gene expression rather than by cytotoxic destruction of virally infected cells. To explore whether Sindbis virus genomes persist in mouse brain after the clearance of infectious virus, we used reverse transcriptasepolymerase chain reaction amplification methods to detect Sindbis virus RNA in brain samples from immunocompetent BALB/c and antibody-treated immunodeficient scid/CB17 mice. RNA sequences from both the nonstructural region (NSP1 gene) and structural regions (E2 gene) of Sindbis virus were detected in the brains of all BALB/c and antibody-treated scid mice examined at 1, 2, and 3 months after infection. Additional BALB/c mouse brains were also positive at 8, 12, and 17 months after infection. To determine whether persistent RNA was capable of resuming unrestricted replication in the absence of the continuous presence of antiviral antibodies, viral titers were measured in the brains ofscid mice at 1, 2, 3, and 6 months after antibody treatment. Viral reactivation was seen in scid mice treated with hyperimmune serum or a low dose of monoclonal antibody to the E2 envelope glycoprotein, but not in mice treated with a high dose of monoclonal antibody to E2. Replication of infectious virus isolated from scid mouse brain could be restricted by repeat treatment with immune serum, indicating that viral reactivation is not due to antibody-escape mutations. These results demonstrate that Sindbis virus can persist long term in a nonproductive form in mouse brain and suggest that the humoral immune response plays an important role in preventing viral reactivation.

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Pathogenesis of encephalitis induced in newborn mice by virulent and avirulent strains of Sindbis virus

Cited by 47 publications

References 29 publications

Interferon regulatory factor 2 protects mice from lethal viral neuroinvasion

Interferon regulatory factor 2 protects mice from lethal viral neuroinvasion

The role of antibody in recovery from alphavirus encephalitis

Persistence of viral RNA in mouse brains after recovery from acute alphavirus encephalitis

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