Chandipura virus induces neuronal death through Fas-mediated extrinsic apoptotic pathway.
J Virol
; 87(22): 12398-406, 2013 Nov.
Article
em En
| MEDLINE
| ID: mdl-24027318
ABSTRACT
Chandipura virus (CHPV; genus Vesiculovirus, family Rhabdoviridae) is an emerging tropical pathogen with a case fatality rate of 55 to 75% that predominantly affects children in the age group of 2 to 16 years. Although it has been established as a neurotropic virus causing encephalitis, the molecular pathology leading to neuronal death is unknown. The present study elucidates for the first time the mechanism of cell death in neurons after CHPV infection that answers the basic cause of CHPV-mediated neurodegeneration. Through various cell death assays in vitro and in vivo, a relationship between viral replication within neuron and neuronal apoptosis has been established. We report that expression of CHPV phosphoprotein increases up to 6 h postinfection and diminishes thereafter in neuronal cell lines, signifying the replicative phase of CHPV. Various analyses conducted during the investigation established that CHPV-infected neurons are undergoing apoptosis through an extrinsic pathway mediated through the Fas-associated death domain (FADD) following activation of caspase-8 and -3 and prominent cleavage of poly(ADP-ribose) polymerase (PARP). Knocking down the expression of caspase-3, the final executioner of apoptosis, in a neuronal cell line by endoribonuclease-prepared small interfering RNA (siRNA) validated its pivotal role in CHPV-mediated neurodegeneration by showing reduction in apoptosis after CHPV infection.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
/
7_ODS3_muertes_prevenibles_nacidos_ninos
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
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Transdução de Sinais
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Proteínas Estruturais Virais
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Apoptose
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Vesiculovirus
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Infecções por Rhabdoviridae
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Proteína de Domínio de Morte Associada a Fas
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Neuroblastoma
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Virol
Ano de publicação:
2013
Tipo de documento:
Article