Whole Genomes of Chandipura Virus Isolates and Comparative Analysis with Other Rhabdoviruses

Abstract

The Chandipura virus (CHPV) belonging to the Vesiculovirus genus and Rhabdoviridae family, has recently been associated with a number of encephalitis epidemics, with high mortality in children, in different parts of India. No full length genome sequences of CHPV isolates were available in GenBank and little is known about the molecular markers for pathogenesis. In the present study, we provide the complete genomic sequences of four isolates from epidemics during 2003–2007. These sequences along with the deduced sequence of the prototype isolate of 1965 were analysed using phylogeny, motif search, homology modeling and epitope prediction methods. Comparison with other rhaboviruses was also done for functional extrapolations. All CHPV isolates clustered with the Isfahan virus and maintained several functional motifs of other rhabdoviruses. A notable difference with the prototype vesiculovirus, Vesicular Stomatitis Virus was in the L-domain flanking sequences of the M protein that are known to be crucial for interaction with host proteins. With respect to the prototype isolate, significant additional mutations were acquired in the 2003–2007 isolates. Several mutations in G mapped onto probable antigenic sites. A mutation in N mapped onto regions crucial for N-N interaction and a putative T-cell epitope. A mutation in the Casein kinase II phosphorylation site in P may attribute to increased rates of phosphorylation. Gene junction comparison revealed changes in the M-G junction of all the epidemic isolates that may have implications on read-through and gene transcription levels. The study can form the basis for further experimental verification and provide additional insights into the virulence determinants of the CHPV.

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

“…It is very intriguing to note that in our investigation, we observed that CHPV belonging to the VSV family is enforcing the extrinsic apoptosis pathway upon infecting the neuronal cells. The plausible reason may be that the CHPV M protein has been reported previously to have very little homology with the VSV M protein (5).…”

“…Extrinsic apoptosis is mediated by the activation of cell surface death receptors belonging to the tumor necrosis factor (TNF) receptor family of proteins, including Fas/APO-1, tumor necrosis factor receptor 1, and TNF-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) and TRAIL-R2 by their cognate ligands, namely, Fas ligand (FasL), TNF, and TRAIL (5,(45)(46)(47). From our qPCR array data, we observed a significant upregulation of FasL mRNA compared to that of our mock-infected control, which suggested that the apoptotic pathway after CHPV infection could be stimulated by the external death domain of FADD.…”

“…Interestingly, its continuing mutating trend has enhanced its lethality to cause human infections unlike its genetic cousin, the vesicular stomatitis virus (VSV). Moreover, its complete genome sequencing has proved that the uniqueness that the virus has acquired is a new threat to humanity (4)(5)(6). Presently, it has been reported that CHPV is more closely related to its Asian kin, the Isfahan virus (ISFV), and also has similarities in sequence with those of the New World viruses, such as Indiana, New Jersey, Alagoas, and Piry viruses, which happen to be different serotypes of VSV (7).…”

“…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). There have been few studies that have identified general pathological mechanisms associated with the infection.…”

Genome sequences published outside of Standards in Genomic Sciences, January-March 2012

“…Aspergillus flavus, sequence accession GSE32177 [79] Bacteriophage SPN3UB, sequence accession JQ288021 [80] Bamboo mitochondria, sequence accession JQ235166 to JQ235179 [81] Boea hygrometrica chloroplast, sequence accession JN107811 [82] Boea hygrometrica mitochondrial, sequence accession JN107812 [82] Canine Picornavirus, sequence accession JN831356 [83] Chandipura virus (CHPV) CIN0327, sequence accession GU212856.1 [84] Chandipura virus (CHPV) CIN0451, sequence accession GU212857.1 [84] Chandipura virus (CHPV) CIN0751, sequence accession GU212858.1 [84] Chandipura virus (CHPV) CIN0755, sequence accession GU190711.1 [84] Chinese Porcine Parvovirus Strain PPV2010, sequence accession JN872448 [85] Common midwife toad megavirus, sequence accession JQ231222 [86] Dengue Virus Serotype 4, sequence accession JN983813 [87] Duck Tembusu Virus, sequence accession JF270480 [88] Duck Tembusu Virus, sequence accession JQ314464 [88] Duck Tembusu Virus, sequence accession JQ314465 [88] Emiliania huxleyi Virus 202, sequence accession HQ634145 [89] Emiliania huxleyi Virus EhV-88, sequence accession JF974310 [89] Emiliania huxleyi EhV-201, sequence accession JF974311 [89] Emiliania huxleyi EhV-207, sequence accession JF974317 [89] Emiliania huxleyi EhV-208, sequence accession JF974318 [89] Glarea lozoyensis, sequence accession GUE00000000 [90] Nannochloropis gaditana, sequence accession AGNI00000000 [91] Oryza sativa cv., sequence accession DRA000499 [92] Partetravirus, sequence accession JN990269 [93] Porcine Bocavirus PBoV5, sequence accession JN831651 [94] Porcine epidemic diarrhea virus, sequence accession JQ282909 [95] Pseudomonas aeruginosa lytic bacteriophage PA1Ø, sequence accession HM624080 [96] Pseudomonas fluorescens phage OBP, sequence accesssion JN627160 [97] RNA Virus from Avocado, sequence accession JN880414 [98] Salmonella enterica Serovar Typhimuriu...…”