Autor(es): Abraham Rachy, Mudaliar Prashant, Jaleel Abdul, Srikanth Jandhyam, Sreekumar Easwaran

Resumo: Global re-emergence of Chikungunya virus (CHIKV) has renewed the interest in its cellular pathogenesis. We subjected CHIKV-infected Human Embryo Kidney cells (HEK293), a widely used cell-based system for CHIKV infection studies, to a high throughput expression proteomics analysis by Liquid Chromatography-t-em mass spectrometry. A total of 1047 differentially expressed proteins were identified in infected cells, consistently in three biological replicates. Proteins involved in transcription, translation, apoptosis - stress response were the major ones among the 209 proteins that had significant up-regulation. In the set of 45 down-regulated proteins, those involved in carbohydrate - lipid metabolism predominated. A STRING network analysis revealed tight interaction of proteins within the apoptosis, stress response - protein synthesis pathways. We short-listed a common set of 30 proteins that can be implicated in cellular pathology of CHIKV infection by comparing our results - results of earlier CHIKV proteomics studies. Modulation of eight proteins selected from this set was re-confirmed at transcript level. One among them, Nucleophosmin, a nuclear chaperone, showed temporal modulation - cytoplasmic aggregation upon CHIKV infection in double immunofluorescence staining - confocal microscopy. The short-listed cellular proteins will be potential c-idates for targeted study of the molecular interactions of CHIKV with host cells. Chikungunya remained as a neglected tropical disease till its re-emergence in 2005 in the La RéUnion isl-s - subsequently, in India - many parts of South East Asia. These - the epidemics that followed in subsequent years ran an explosive course leading to extreme morbidity - attributed mortality to this originally benign virus infection. Apart from classical symptoms of acute fever - debilitating polyarthralgia lasting for several weeks, a number of complications were documented. These included aphthous-like ulcers - vesiculo-bullous eruptions on the skin, hepatic involvement, central nervous system complications such as encephalopathy - encephalitis, - transplacental transmission. The disease has recently spread to the Americas with its initial documentation in the Caribbean isl-s. The Asian genotype of this positive-str-ed RNA virus of the Alphavirus genus has been attributed in these outbreaks. However, the disease ran a similar course as the one caused by the East, Central - South African (ECSA) genotype in the other parts of the world. Studies have documented a number of mutations in the re-emerging strains of the virus that enhances mosquito adaptability - modulates virus infectivity. This might support the occurrence of fiery outbreaks in the absence of herd immunity in affected population. Several research groups work to underst- the pathogenesis of chikungunya - the mechanisms of complications using cellular - animal models. A few proteomics approaches have been employed earlier to underst- the protein level changes in the infected cells. Our present study, which couples a high throughput proteomic analysis - a comparative review of these earlier studies, identifies a few critical molecules as hypothetical c-idates that might be important in this infection - for future study.

Palavras-Chave: Chikungunya virus; Differential expression; LC-MS/MS; Shotgun proteomics

Imprenta: Journal of Proteomics, v. 120, p. 126-141, 2015

Identificador do objeto digital: 10.1016/j.jprot.2015.03.007

Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Protein synthesis ; Chikungunya virus - Proteins ; Chikungunya virus - Proteome ; Chikungunya virus - RNA ; Chikungunya virus - Viral infections ; Chikungunya virus - Molecular methods ; Chikungunya Virus - Virus ; Chikungunya virus - Molecular screening ; Chikungunya virus - Transmission ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Epidemic

Data de publicação: 2015

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