Pathogenesis and Diseases of the Central Nervous System Caused by Murine Coronaviruses

Dales, Samuel; Anderson, Robert

doi:10.1007/978-1-4899-1531-3_13

Cited by 4 publications

(3 citation statements)

References 220 publications

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“…MHV infections exhibit remarkable variability in cytopathology, ranging from acutely cytolytic to essentially asymptomatic levels in cultured cells (13,42). This range of MHV-induced cytopathology has generally been considered to be dependent on the variable activity of the S protein.…”

Section: Discussionmentioning

confidence: 99%

Intracellular Complexes of Viral Spike and Cellular Receptor Accumulate during Cytopathic Murine Coronavirus Infections

Rao

Gallagher

1998

J Virol

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Murine hepatitis virus (MHV) infections exhibit remarkable variability in cytopathology, ranging from acutely cytolytic to essentially asymptomatic levels. In this report, we assess the role of the MHV receptor (MHVR) in controlling this variable virus-induced cytopathology. We developed human (HeLa) cell lines in which the MHVR was produced in a regulated fashion by placing MHVR cDNA under the control of an inducible promoter. Depending on the extent of induction, MHVR levels ranged from less than ϳ1,500 molecules per cell (designated R lo ) to ϳ300,000 molecules per cell (designated R hi ). Throughout this range, the otherwise MHV-resistant HeLa cells were rendered susceptible to infection. However, infection in the R lo cells occurred without any overt evidence of cytopathology, while the corresponding R hi cells died within 14 h after infection. When the HeLa-MHVR cells were infected with vaccinia virus recombinants encoding MHV spike (S) proteins, the R hi cells succumbed within 12 h postinfection; R lo cells infected in parallel were intact, as judged by trypan blue exclusion. This acute cytopathology was not due solely to syncytium formation between the cells producing S and MHVR, because fusion-blocking antiviral antibodies did not prevent it. These findings raised the possibility of an intracellular interaction between S and MHVR in the acute cell death. Indeed, we identified intracellular complexes of S and MHVR via coimmunoprecipitation of endoglycosidase H-sensitive forms of the two proteins. We suggest that MHV infections can become acutely cytopathic once these intracellular complexes rise above a critical threshold level.

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Section: Discussionmentioning

confidence: 99%

Intracellular Complexes of Viral Spike and Cellular Receptor Accumulate during Cytopathic Murine Coronavirus Infections

Rao

Gallagher

1998

J Virol

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“…The murine coronavirus mouse hepatitis virus JHM (MHV-JHM) causes acute and chronic neurological disease upon infection of the central nervous system (CNS) of susceptible rodents and has been intensively studied as an experimental model of human demyelinating diseases such as multiple sclerosis (10,16,34). The type of disease induced by MHV-JHM depends on the strain of virus, the age and type of animal, the amount of virus and route of inoculation, the host immune status, and other experimental variables.…”

mentioning

confidence: 99%

Evolution of mouse hepatitis virus: detection and characterization of spike deletion variants during persistent infection

Rowe

Baker

Nathan

et al. 1997

J Virol

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High-frequency RNA recombination has been proposed as an important mechanism for generating viral deletion variants of murine coronavirus. Indeed, a number of variants with deletions in the spike glycoprotein have been isolated from persistently infected animals. However, the significance of generating and potentially accumulating deletion variants in the persisting viral RNA population is unclear. To study this issue, we evaluated the evolution of spike variants by examining the population of spike RNA sequences detected in the brains and spinal cords of mice inoculated with coronavirus and sacrificed at 4, 42, or 100 days postinoculation. We focused on the S1 hypervariable region since previous investigators had shown that this region is subject to recombination and deletion. RNA isolated from the brains or spinal cords of infected mice was rescued by reverse transcription-PCR, and the amplified products were cloned and used in differential colony hybridizations to identify individual isolates with deletions. We found that 11 of 20 persistently infected mice harbored spike deletion variants (SDVs), indicating that deletions are common but not required for persistent infection. To determine if a specific type of SDV accumulated during persistence, we sequenced 106 of the deletion isolates. We identified 23 distinct patterns of SDVs, including 5 double-deletion variants. Furthermore, we found that each mouse harbored distinct variants in its central nervous system (CNS), suggesting that SDVs are generated during viral replication in the CNS. Interestingly, mice with the most severe and persisting neurological disease harbored the most prevalent and diverse quasispecies of SDVs. Overall, these findings illustrate the complexity of the population of persisting viral RNAs which may contribute to chronic disease.

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“…The proventriculus is a cranial glandular compartment of the stomach, adjacent to the gizzard, which is the caudal muscular compartment. demyelination [210], reviewed by Dales and Anderson [219], Stohlman and Hinton, [220] and Matthews et al [221]. A number of enveloped and nonenveloped, RNA and DNA viruses have been associated with demyelination in humans and rodents, including coronaviruses [220].…”

Section: Tropisms Of Coronavirusesmentioning

confidence: 99%

Coronaviridae: a review of coronaviruses and toroviruses

Cavanagh

2005

Coronaviruses With Special Emphasis on First Insights Concerning SARS

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Pathogenesis and Diseases of the Central Nervous System Caused by Murine Coronaviruses

Cited by 4 publications

References 220 publications

Intracellular Complexes of Viral Spike and Cellular Receptor Accumulate during Cytopathic Murine Coronavirus Infections

Intracellular Complexes of Viral Spike and Cellular Receptor Accumulate during Cytopathic Murine Coronavirus Infections

Evolution of mouse hepatitis virus: detection and characterization of spike deletion variants during persistent infection

Coronaviridae: a review of coronaviruses and toroviruses

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