Tags

Type your tag names separated by a space and hit enter

Coxsackievirus B3 and the neonatal CNS: the roles of stem cells, developing neurons, and apoptosis in infection, viral dissemination, and disease.
Am J Pathol. 2003 Oct; 163(4):1379-93.AJ

Abstract

Neonates are particularly susceptible to coxsackievirus infections of the central nervous system (CNS), which can cause meningitis, encephalitis, and long-term neurological deficits. However, viral tropism and mechanism of spread in the CNS have not been examined. Here we investigate coxsackievirus B3 (CVB3) tropism and pathology in the CNS of neonatal mice, using a recombinant virus expressing the enhanced green fluorescent protein (eGFP). Newborn pups were extremely vulnerable to coxsackievirus CNS infection, and this susceptibility decreased dramatically by 7 days of age. Twenty-four hours after intracranial infection of newborn mice, viral genomic RNA and viral protein expression were detected in the choroid plexus, the olfactory bulb, and in cells bordering the cerebral ventricles. Many of the infected cells bore the anatomical characteristics of type B stem cells, which can give rise to neurons and astrocytes, and expressed the intermediate filament protein nestin, a marker for progenitor cells. As the infection progressed, viral protein was identified in the brain parenchyma, first in cells expressing neuron-specific class III beta-tubulin, an early marker of neuronal differentiation, and subsequently in cells expressing NeuN, a marker of mature neurons. At later time points, viral protein expression was restricted to neurons in specific regions of the brain, including the hippocampus, the entorhinal and temporal cortex, and the olfactory bulb. Extensive neuronal death was visible, and appeared to result from virus-induced apoptosis. We propose that the increased susceptibility of the neonatal CNS to CVB infection may be explained by the virus' targeting neonatal stem cells; and that CVB is carried into the brain parenchyma by developing neurons, which continue to migrate and differentiate despite the infection. On full maturation, some or all of the infected neurons undergo apoptosis, and the resulting neuronal loss can explain the longer-term clinical picture.

Authors+Show Affiliations

Scripps Research Institute, La Jolla, California 92037, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14507646

Citation

Feuer, Ralph, et al. "Coxsackievirus B3 and the Neonatal CNS: the Roles of Stem Cells, Developing Neurons, and Apoptosis in Infection, Viral Dissemination, and Disease." The American Journal of Pathology, vol. 163, no. 4, 2003, pp. 1379-93.
Feuer R, Mena I, Pagarigan RR, et al. Coxsackievirus B3 and the neonatal CNS: the roles of stem cells, developing neurons, and apoptosis in infection, viral dissemination, and disease. Am J Pathol. 2003;163(4):1379-93.
Feuer, R., Mena, I., Pagarigan, R. R., Harkins, S., Hassett, D. E., & Whitton, J. L. (2003). Coxsackievirus B3 and the neonatal CNS: the roles of stem cells, developing neurons, and apoptosis in infection, viral dissemination, and disease. The American Journal of Pathology, 163(4), 1379-93.
Feuer R, et al. Coxsackievirus B3 and the Neonatal CNS: the Roles of Stem Cells, Developing Neurons, and Apoptosis in Infection, Viral Dissemination, and Disease. Am J Pathol. 2003;163(4):1379-93. PubMed PMID: 14507646.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Coxsackievirus B3 and the neonatal CNS: the roles of stem cells, developing neurons, and apoptosis in infection, viral dissemination, and disease. AU - Feuer,Ralph, AU - Mena,Ignacio, AU - Pagarigan,Robb R, AU - Harkins,Stephanie, AU - Hassett,Daniel E, AU - Whitton,J Lindsay, PY - 2003/9/26/pubmed PY - 2003/10/30/medline PY - 2003/9/26/entrez SP - 1379 EP - 93 JF - The American journal of pathology JO - Am J Pathol VL - 163 IS - 4 N2 - Neonates are particularly susceptible to coxsackievirus infections of the central nervous system (CNS), which can cause meningitis, encephalitis, and long-term neurological deficits. However, viral tropism and mechanism of spread in the CNS have not been examined. Here we investigate coxsackievirus B3 (CVB3) tropism and pathology in the CNS of neonatal mice, using a recombinant virus expressing the enhanced green fluorescent protein (eGFP). Newborn pups were extremely vulnerable to coxsackievirus CNS infection, and this susceptibility decreased dramatically by 7 days of age. Twenty-four hours after intracranial infection of newborn mice, viral genomic RNA and viral protein expression were detected in the choroid plexus, the olfactory bulb, and in cells bordering the cerebral ventricles. Many of the infected cells bore the anatomical characteristics of type B stem cells, which can give rise to neurons and astrocytes, and expressed the intermediate filament protein nestin, a marker for progenitor cells. As the infection progressed, viral protein was identified in the brain parenchyma, first in cells expressing neuron-specific class III beta-tubulin, an early marker of neuronal differentiation, and subsequently in cells expressing NeuN, a marker of mature neurons. At later time points, viral protein expression was restricted to neurons in specific regions of the brain, including the hippocampus, the entorhinal and temporal cortex, and the olfactory bulb. Extensive neuronal death was visible, and appeared to result from virus-induced apoptosis. We propose that the increased susceptibility of the neonatal CNS to CVB infection may be explained by the virus' targeting neonatal stem cells; and that CVB is carried into the brain parenchyma by developing neurons, which continue to migrate and differentiate despite the infection. On full maturation, some or all of the infected neurons undergo apoptosis, and the resulting neuronal loss can explain the longer-term clinical picture. SN - 0002-9440 UR - https://www.unboundmedicine.com/medline/citation/14507646/Coxsackievirus_B3_and_the_neonatal_CNS:_the_roles_of_stem_cells_developing_neurons_and_apoptosis_in_infection_viral_dissemination_and_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9440(10)63496-7 DB - PRIME DP - Unbound Medicine ER -