Emerging Viral Infections of the Central Nervous System

Tyler, Kenneth L.

doi:10.1001/archneurol.2009.153

Cited by 109 publications

(61 citation statements)

References 143 publications

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“…These diseases can severely affect human health and can be associated with long-term sequelae. In addition, new neurotropic viruses are continually emerging and can challenge the nervous system in new ways 5,6 (BOX 1). Emerging viruses are particularly problematic because they are often less equilibrated with their new host, and they can spread rapidly and induce severe pathology.…”

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confidence: 99%

“…Recently, West Nile virus (WNV) spread into humans living in North America, resulting in the development of encephalitis, meningitis and acute flaccid paralysis in a portion of the infected population 6 . Although the exact route by which WNV first entered humans is unknown, it is considered likely that migratory birds (which serve as the normal host reservoir) and mosquito vectors participated in its dissemination.…”

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confidence: 99%

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Illuminating viral infections in the nervous system

2011

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Viral infections are a major cause of human disease. Although most viruses replicate in peripheral tissues, some have developed unique strategies to move into the nervous system, where they establish acute or persistent infections. Viral infections in the central nervous system (CNS) can alter homeostasis, induce neurological dysfunction and result in serious, potentially life-threatening inflammatory diseases. This Review focuses on the strategies used by neurotropic viruses to cross the barrier systems of the CNS and on how the immune system detects and responds to viral infections in the CNS. A special emphasis is placed on immune surveillance of persistent and latent viral infections and on recent insights gained from imaging both protective and pathogenic antiviral immune responses.

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confidence: 99%

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Illuminating viral infections in the nervous system

2011

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“…Lymphocytic choriomeningitis virus (LCMV) is a bisegmented ssRNA virus belonging to the Arenaviridae and is considered an emerging human pathogen (13). Human transmission has been shown to occur in utero, upon transplantation with infected organs, or upon contact with infected laboratory and wild animals.…”

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confidence: 99%

IRF7-Dependent Type I Interferon Production Induces Lethal Immune-Mediated Disease in STAT1 Knockout Mice Infected with Lymphocytic Choriomeningitis Virus

Höfer

Jung

et al. 2014

J Virol

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Following systemic infection with lymphocytic choriomeningitis virus (LCMV), STAT1 knockout (KO) mice but not wild-type, STAT2 KO, IRF9 KO, or IFNAR KO mice develop lethal disease perpetrated by CD4؉ T cells. IRF7 is a key transcriptional activator of type I IFN (IFN-I) during LCMV infection. Here, the role of IRF7 in the lethal host response to LCMV infection in STAT1 KO mice was examined. In contrast to STAT1 KO mice, STAT1/IRF7 double KO (DKO) mice survived LCMV infection with a reduced immune pathology in key organs, such as the liver and spleen. However, similar to STAT1 KO mice, STAT1/IRF7 DKO mice failed to control LCMV replication and spread. LCMV infection in STAT1 KO mice was associated with a significant elevation in the levels of a number of cytokines in serum, including IFN-Is, but this was largely absent in STAT1/IRF7 DKO mice, which had a modest increase in the levels of gamma interferon and CCL2 only. Since IRF7 is known to be a key transcriptional regulator of IFN-I gene expression, the possible role of IFN-I in lethal disease was examined further. STAT1/IFNAR DKO mice, in contrast to STAT1 KO mice, all survived infection with LCMV and exhibited little tissue immune pathology. Additionally, STAT1 KO mice that were deficient for either of the two IFN-I signaling molecules, STAT2 or IRF9, also survived LCMV infection. We conclude that the lethal immune-mediated disease resulting from LCMV infection in STAT1 KO mice is (i) dependent on IRF7-induced IFN-I production and (ii) driven by noncanonical IFN-I signaling via STAT2 and IRF9. IMPORTANCEHere we report on the basis for the novel, fatal immune-mediated disease of STAT1 KO mice infected with LCMV. Our findings show that, surprisingly, the pathogenesis of this disease is dependent on IRF7-mediated type I interferon production. Moreover, our study identifies noncanonical type I interferon signaling via STAT2 and IRF9 to be essential for the type I IFN-driven fatal disease in LCMV-infected STAT1 KO mice. These results further highlight the significance of noncanonical type I IFN signaling in the pathogenesis of host-mediated injury following viral infection.

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“…Lymphocytic choriomeningitis virus (LCMV), a bisegmented ssRNA virus belonging to the Arenaviridae family, is considered an emerging human pathogen (Tyler, 2009). LCMV infection in its natural host, i.e., the mouse, is a widely studied model for virus host interactions that has contributed to the understanding of immune tolerance, immunodominance, MHC restriction, viral-immune interactions and the basis for viral persistence (Buchmeier et al, 1980;Kang and McGavern, 2008).…”

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confidence: 99%

Analgesia in mice with experimental meningitis reduces pain without altering immune parameters

Mundt

Groettrup

Basler

2015

ALTEX

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SummaryIntracranial lymphocytic choriomeningitis virus (LCMV) infection is a widely used animal model to study virus-induced cytotoxic T cell (CTL) mediated meningitis and immunopathology. This model causes severe pain and distress in mice, especially at later stages of the disease. Therefore, new treatment regimens to improve animal welfare have to be developed. In this study, we subcutaneously implanted ALZET ® osmotic pumps continuously releasing buprenorphine to reduce pain in mice with LCMV-induced meningitis. Mice treated with buprenorphine demonstrated strongly reduced symptoms of pain. The LCMV-specific cytotoxic T cell response and the immune cell infiltration into the central nervous system (CNS) were unchanged in analgesia treated mice, indicating that the LCMV-induced immune response was not altered in these mice. Taken together, we demonstrate that in this animal model for meningitis continuous buprenorphine treatment improves animal welfare without affecting the immune response.

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Emerging Viral Infections of the Central Nervous System

Cited by 109 publications

References 143 publications

Illuminating viral infections in the nervous system

Illuminating viral infections in the nervous system

IRF7-Dependent Type I Interferon Production Induces Lethal Immune-Mediated Disease in STAT1 Knockout Mice Infected with Lymphocytic Choriomeningitis Virus

Analgesia in mice with experimental meningitis reduces pain without altering immune parameters

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