Autor(es)Rathore Abhay P S,Haystead Timothy,Das Pratyush K,Merits -res,Ng Mah-Lee,Vasudevan Subhash G

ResumoThe global emergence of Chikungunya virus (CHIKV) infection is alarming - currently there is no licensed vaccine or antiviral treatment available to mitigate this disease. CHIKV infection typically results in high viral load with an outcome of high fever, skin rashes, muscle pain, - sequelae of prolonged arthritis, which occurs in >90% of the infected cases. In this study, using biochemical pull-downs, mass-spectrometry, - microscopic imaging techniques, we have identified novel interactions between CHIKV nsP3 or nsP4 proteins with the host stress-pathway chaperone HSP-90 protein. Indeed, silencing of HSP-90 transcripts using siRNA disrupts CHIKV replication in cultured cells. Furthermore, drugs targeting HSP-90, such as commercially available geldanamycin, as well as other specific HSP-90 inhibitor drugs that had been obtained from a purinome mining approach (HS-10 - SNX-2112) showed dramatic reduction in viral titers - reduced inflammation in a CHIKV mouse model of severe infection - musculopathy. The detailed study of the underlying molecular mechanism of these viral - host protein interactions may provide a platform to develop novel therapeutics against CHIKV infection.

Palavras-ChaveCHIKV mouse model; CHIKV nsP3; CHIKV nsP4; Geldanamycin; HSP-90; Protein interactions

ImprentaAntiviral Research, v. 103, p. 7-16, 2014

DescritoresChikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Infectious diseases ; Chikungunya virus - Inflammation ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever

Data de Publicação:2014