Chemokine profiling of Japanese encephalitis virus-infected mouse neuroblastoma cells by microarray and real-time RT-PCR: implication in neuropathogenesis.
Japanese encephalitis (JE) is one of the leading causes of acute encephalopathy affecting children and adolescents in the tropics. JE virus (JEV) infection causes prominent neurological sequelae in approximately one-third of the survivors. In humans, the inflammatory response of CNS consequent to JEV induced viral encephalitis is mediated through chemokines released by various cells of CNS. In the present study, the chemokine profiles of mouse neuroblastoma cells (N2A) following JEV infection was analyzed by cDNA microarray followed by real-time RT-PCR. Eighty mRNA transcripts belonging to various functional classes exhibited significant alterations in gene expression. There was considerable induction of genes involved in apoptosis and anti-viral response. Modified levels of several transcripts involved in proinflammatory and anti-inflammatory processes exemplified the balance between opposing forces during JEV pathogenesis. Other genes displaying altered transcription included those associated with host translation, cellular metabolism, cell cycle, signal transduction, transcriptional regulation, protein trafficking, neurotransmitters, neuron maturation, protein modulators, ER stress and cytoskeletal proteins. The infection of neurons results in the synthesis of proinflammatory chemokines, which are early important mediators of leukocyte recruitment to sites of viral infection. Our results clearly suggest the implication of chemokines in neuropathogenesis of JEV infection leading to neurological sequelae. Pro- and anti-inflammatory agents targeted against chemokines such as CXCL10 may provide possible therapeutic modalities that can mitigate the morbidity associated with JEV infection of the CNS.
Gupta
Nimesh
N
Division of Virology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, India.
Santhosh
S R
SR
Babu
J Pradeep
JP
Parida
M M
MM
Rao
P V Lakshmana
PV
D000818:Animals; D045744:Cell Line, Tumor; D018925:Chemokines / Q000096:biosynthesis*; D004664:Encephalitis Virus, Japanese / Q000276:immunology*; D020869:Gene Expression Profiling; D051379:Mice; D008853:Microscopy; D009474:Neurons / Q000276:immunology* / Q000821:virology*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D010948:Viral Plaque Assay
D018925:Chemokines