Chandipura Virus: An emerging tropical pathogen

Menghani, Sunil; Chikhale, Rupesh; Raval, Ami P.; Wadibhasme, Pankaj G.; Khedekar, Pramod B.

doi:10.1016/j.actatropica.2012.06.001

Cited by 54 publications

(34 citation statements)

References 123 publications

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“…CHPV has been reported to be an emerging human pathogen in the Indian subcontinent, with a fatality rate of around 55 to 77% (8)(9)(10)(11). Children below 15 years of age are more vulnerable than adults, who show symptoms similar to those of any other encephalitis, such as high-grade fever, vomiting, altered sensorium, generalized convulsions, decerebrate posture, and grade IV coma (8,12).…”

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confidence: 99%

“…and Sergentomyia spp. have been reported to be the major carriers of CHPV during the outbreaks in recent years (10,13). CHPV is a negative-stranded enveloped RNA virus with an approximate genome length of 11 kb, comprised of 5 genes which encode a glycoprotein (G), a matrix protein (M), a nucleoprotein (N), a phosphoprotein (P protein), and a large polymerase protein (L) that helps the virus successfully enter the host and replicate (5,(14)(15)(16).…”

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confidence: 99%

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Chandipura Virus Induces Neuronal Death through Fas-Mediated Extrinsic Apoptotic Pathway

Ghosh

Dutta

Basu

2013

J Virol

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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.

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confidence: 99%

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confidence: 99%

Chandipura Virus Induces Neuronal Death through Fas-Mediated Extrinsic Apoptotic Pathway

Ghosh

Dutta

Basu

2013

J Virol

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“…The cause of death was interpreted as encephalitis, acute catastrophic event in the brain, spasm or transient obstruction due to vasculitis. However, none of these could be confirmed scientifically3. The presence of CHPV in the brain biopsy specimens as detected by immunofluorescent antibody technique during the early investigations pointed towards the probable association of CHPV4.…”

Section: Introductionmentioning

confidence: 96%

“…Chandipura virus (CHPV), an arbovirus belonging to genus Vesiculovirus in the family Rhabdoviridae has gained global attention as an encephalitis causing virus after the 2003-2004 outbreaks in central India12345. A total of 322 child deaths; 183 in Andhra Pradesh (AP), 115 in Maharashtra and 24 in Gujarat were reported during the outbreaks.…”

Section: Introductionmentioning

confidence: 99%

Changing clinical scenario in Chandipura virus infection

Sudeep¹,

Gurav²,

Bondre³

2016

Indian Journal of Medical Research

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Chandipura virus (CHPV) (Vesiculovirus: Rhabdoviridae) garnered global attention as an emerging neurotropic pathogen inflicting high mortality in children within 24 h of commencement of symptoms. The 2003-2004 outbreaks in Central India witnessed case fatality rates ranging from 56-75 per cent in Andhra Pradesh and Gujarat with typical encephalitic symptoms. Due to the acute sickness and rapid deterioration, the precise mechanism of action of the virus is still unknown. Recent studies have shown increased expression of CHPV phosphoprotein upto 6 h post infection (PI) demonstrating CHPV replication in neuronal cells and the rapid destruction of the cells by apoptosis shed light on the probable mechanism of rapid death in children.Phlebotomine sandflies are implicated as vectors due to their predominance in endemic areas, repeated virus isolations and their ability to transmit the virus by transovarial and venereal routes. Significant contributions have been made in the development of diagnostics and prophylactics, vaccines and antivirals. Two candidate vaccines, viz. a recombinant vaccine and a killed vaccine and siRNAs targeting P and M proteins have been developed and are awaiting clinical trials. Rhabdomyosarcoma and Phlebotomus papatasi cell lines as well as embryonated chicken eggs have been found useful in virus isolation and propagation. Despite these advancements, CHPV has been a major concern in Central India and warrants immediate attention from virologists, neurologists, paediatricians and the government for containing the virus.

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“…We decided to investigate interactions between LMP2 and the M protein of Chandipura virus (CHAV), a vesiculovirus responsible for deadly encephalitis in children mainly in India (33), or spring viremia of carp virus (SVCV), a more distant member of the same genus (34). Coimmunoprecipitations were performed on lysates of N2A cells that had previously been transfected with HA-LMP2 together with either pmyc-M VSV, pmyc-M CHAV, or pmyc-M SVCV.…”

Section: Identification Of Lmp2 As a Binding Partner Of Vsv Matrix Prmentioning

confidence: 99%

Characterization of the Interaction between the Matrix Protein of Vesicular Stomatitis Virus and the Immunoproteasome Subunit LMP2

Beilstein

Obiang

Raux

et al. 2015

J Virol

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The matrix protein (M) of vesicular stomatitis virus (VSV) is involved in virus assembly, budding, gene regulation, and cellular pathogenesis. Using a yeast two-hybrid system, the M globular domain was shown to interact with LMP2, a catalytic subunit of the immunoproteasome (which replaces the standard proteasome catalytic subunit PSMB6). The interaction was validated by coimmunoprecipitation of M and LMP2 in VSV-infected cells. The sites of interaction were characterized. A single mutation of M (I96A) which significantly impairs the interaction between M and LMP2 was identified. We also show that M preferentially binds to the inactive precursor of LMP2 (bearing an N-terminal propeptide which is cleaved upon LMP2 maturation). Furthermore, taking advantage of a sequence alignment between LMP2 and its proteasome homolog, PSMB6 (which does not bind to M), we identified a mutation (L45R) in the S1 pocket where the protein substrate binds prior to cleavage and a second one (D17A) of a conserved residue essential for the catalytic activity, resulting in a reduction of the level of binding to M. The combination of both mutations abolishes the interaction. Taken together, our data indicate that M binds to LMP2 before its incorporation into the immunoproteasome. As the immunoproteasome promotes the generation of major histocompatibility complex (MHC) class I-compatible peptides, a feature which favors the recognition and the elimination of infected cells by CD8 T cells, we suggest that M, by interfering with the immunoproteasome assembly, has evolved a mechanism that allows infected cells to escape detection and elimination by the immune system. IMPORTANCEThe immunoproteasome promotes the generation of MHC class I-compatible peptides, a feature which favors the recognition and the elimination of infected cells by CD8 T cells. Here, we report on the association of vesicular stomatitis virus (VSV) matrix protein (M) with LMP2, one of the immunoproteasome-specific catalytic subunits. M preferentially binds to the LMP2 inactive precursor. The M-binding site on LMP2 is facing inwards in the immunoproteasome and is therefore not accessible to M after its assembly. Hence, M binds to LMP2 before its incorporation into the immunoproteasome. We suggest that VSV M, by interfering with the immunoproteasome assembly, has evolved a mechanism that allows infected cells to escape detection and elimination by the immune system. Modulating this M-induced immunoproteasome impairment might be relevant in order to optimize VSV for oncolytic virotherapy. V esicular stomatitis virus (VSV) is the prototype rhabdovirus and for years has been used as a model to study many aspects of the virus life cycle. Its negative-strand RNA genome of 11,161 nucleotides successively encodes the nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G), and the RNAdependent RNA polymerase (L). The N, P, and L proteins are associated with the RNA molecule and compose the transcriptionally active nucleocapsid (NC). The NC is enveloped by...

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Chandipura Virus: An emerging tropical pathogen

Cited by 54 publications

References 123 publications

Chandipura Virus Induces Neuronal Death through Fas-Mediated Extrinsic Apoptotic Pathway

Chandipura Virus Induces Neuronal Death through Fas-Mediated Extrinsic Apoptotic Pathway

Changing clinical scenario in Chandipura virus infection

Characterization of the Interaction between the Matrix Protein of Vesicular Stomatitis Virus and the Immunoproteasome Subunit LMP2

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