Cooperation of B cells and T cells is required for survival of mice infected with vesicular stomatitis virus

Thomsen, Allan Randrup; Nansen, Anneline; Andersen, Camilla; Johansen, J; Marker, O; Christensen, Jan Pravsgaard

doi:10.1093/intimm/9.11.1757

Cited by 79 publications

(82 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is assumed that clearance of RNA viruses from neurons is initiated by the expression of IFN-␤ and that it is primarily mediated by neutralizing Abs that effectively inhibit the production of new virus but do not necessarily eliminate virus RNA from cells. This concept is in line with the observation that CD4-depleted WT mice, which mount only short-lived neutralizing Ab responses, show an increased susceptibility to lethal VSV infection (14,37).…”

Section: Discussionsupporting

confidence: 79%

See 1 more Smart Citation

Local Type I IFN Receptor Signaling Protects against Virus Spread within the Central Nervous System

Detje

Meyer

Schmidt

et al. 2009

The Journal of Immunology

137

144

View full text Add to dashboard Cite

Several neurotropic viruses such as vesicular stomatitis virus (VSV) induce peripheral neutralizing Ab responses and still can infect cells within the CNS. To address whether local type I IFN receptor (IFNAR) triggering plays a role in controlling virus replication within the brain, we generated mice with a cell type-specific IFNAR deletion in neuroectodermal cells of the CNS (NesCre+/−IFNARflox/flox). Intranasal VSV infection with 103 PFU was well tolerated by wild-type mice, whereas conventional IFNAR−/− mice died within 2–3 days. In contrast, brain-specific NesCre+/−IFNARflox/flox mice survived until day 5–6 and then became hemiplegic and died. Terminally ill NesCre+/−IFNARflox/flox mice showed 10- to 100-fold higher virus loads in the brain than IFNAR−/− mice, whereas little or no virus was found in other organs. In wild-type animals, virus could be reisolated only from the olfactory bulb until day 6 where also STAT1 activation as a measure of IFNAR triggering was detected. Virus infection was found exclusively in glomerular structures of the olfactory bulb, whereas surrounding cells that showed STAT1 phosphorylation as a measure of IFNAR trigging were free of virus. Our data indicate that upon intranasal VSV instillation, early and localized IFNAR triggering in the glomerular layer of the olfactory bulb is critically required to prevent viral spread over the entire CNS and thus confers survival.

show abstract

Section: Discussionsupporting

confidence: 79%

“…These observations are in line with a previous study also showing that MHC class I-deficient mice showed a similar disease course upon i.n. VSV infection compared with WT mice (37). However, another study showed that in the absence of CD8 ϩ T cells, a reduced survival of VSV infection was observed (3).…”

Section: Discussionmentioning

confidence: 99%

Local Type I IFN Receptor Signaling Protects against Virus Spread within the Central Nervous System

Detje

Meyer

Schmidt

et al. 2009

The Journal of Immunology

137

144

View full text Add to dashboard Cite

show abstract

“…Although cytotoxic T cell responses are generally considered to be critical for resolving viral infections, substantial evidence indicates that it is the antibodies that play an indispensable role in the early phase of VSV infection. For example, B cell-de cient mice are highly susceptible to low doses of virus, although mortality can be prevented by transferring naive B cells to the mice before challenge as well as by administering immune serum after challenge (15)(16)(17). The type-speci c VSV G protein is the viral antigen giving rise to the neutralizing antibodies that are critically important in eliminating VSV infection.…”

Section: Resultsmentioning

confidence: 99%

Vesicular Stomatitis Virus (VSV) Therapy of Tumors

2000

View full text Add to dashboard Cite

SummaryVesicular stomatitis virus (VSV) is an essentially nonpathogeni c negative-stranded RNA virus, the replication of which is extremely sensitive to the antiviral effects of interferon (IFN). We demonstrate here that VSV selectively induces the cytolysis of numerous transformed human cell lines in vitro, with all the morphological characteristics of apoptotic cell death. Importantly, VSV can also potently inhibit the growth of p53-null C6 glioblastoma tumors in vivo without infecting and replicating in normal tissue. With our previous ndings demonstrating that primary cells containing the doublestranded RNA-activated protein kinase PKR and a functional IFN system are not permissive to VSV replication, these results suggest that signaling by IFN may be defective in many malignancies. Thus VSV might be useful in novel therapeutic strategies for targeting neoplastic disease. IUBMB Life, 50: 135 -138, 2000

show abstract

“…Semliki Forest virus clearance is delayed several weeks in the absence of B cells (47). In addition, Sindbis virus is cleared from the CNS of immunodeficient mice by transferred B cells, but not T cells (19), and vesicular stomatitis virus is acutely lethal in B cell-deficient mice (48). Collectively, these results suggest that B cells are required for clearance of some primary viral infections, although the mechanisms of B cell activity may differ depending on the pathogen.…”

Section: Discussionmentioning

confidence: 95%

“…Therefore, the liver is not inherently resistant to MHV-A59 persistence, and the immune response is implicated to account for the difference observed between the liver and the CNS in the absence of B cells. Interestingly, other viruses that require B cells for clearance, including Sindbis, vesicular stomatitis virus, HSV-1, Semliki Forest virus, and LCMV, also infect the CNS (18,19,(47)(48)(49). The CNS environment may directly favor a dependency on B cells, perhaps by down-regulation of T lymphocyte function.…”

Section: Discussionmentioning

confidence: 99%

Antibody Is Required for Clearance of Infectious Murine Hepatitis Virus A59 from the Central Nervous System, But Not the Liver

Matthews

Weiss

Shlomchik

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

Intracerebral inoculation with mouse hepatitis virus strain A59 results in viral replication in the CNS and liver. To investigate whether B cells are important for controlling mouse hepatitis virus strain A59 infection, we infected muMT mice who lack membrane-bound IgM and therefore mature B lymphocytes. Infectious virus peaked and was cleared from the livers of muMT and wild-type mice. However, while virus was cleared from the CNS of wild-type mice, virus persisted in the CNS of muMT mice. To determine how B cells mediate viral clearance, we first assessed CD4+ T cell activation in the absence of B cells as APC. CD4+ T cells express wild-type levels of CD69 after infection in muMT mice. IFN-γ production in response to viral Ag in muMT mice was also normal during acute infection, but was decreased 31 days postinfection compared with that in wild-type mice. The role of Ab in viral clearance was also assessed. In wild-type mice plasma cells appeared in the CNS around the time that virus is cleared. The muMT mice that received A59-specific Ab had decreased virus, while mice with B cells deficient in Ab secretion did not clear virus from the CNS. Viral persistence was not detected in FcR or complement knockout mice. These data suggest that clearance of infectious mouse hepatitis virus strain A59 from the CNS requires Ab production and perhaps B cell support of T cells; however, virus is cleared from the liver without the involvement of Abs or B cells.

show abstract

Cooperation of B cells and T cells is required for survival of mice infected with vesicular stomatitis virus

Cited by 79 publications

References 34 publications

Local Type I IFN Receptor Signaling Protects against Virus Spread within the Central Nervous System

Local Type I IFN Receptor Signaling Protects against Virus Spread within the Central Nervous System

Vesicular Stomatitis Virus (VSV) Therapy of Tumors

Antibody Is Required for Clearance of Infectious Murine Hepatitis Virus A59 from the Central Nervous System, But Not the Liver

Contact Info

Product

Resources

About