Autor(es)Rathore Abhay P S, Ng Mah-Lee, Vasudevan Subhash G

ResumoChikungunya (CHIKV) - Sindbis (SINV) are arboviruses belonging to the alphavirus genus within the Togaviridae family. They cause frequent epidemics of febrile illness - long-term arthralgic sequelae that affect millions of people each year. Both viruses replicate prodigiously in infected patients - in vitro in mammalian cells, suggesting some level of control over the host cellular translational machinery that senses - appropriately directs the cell's fate through the unfolded protein response (UPR). The mammalian UPR involves BIP (or GRP78), the master sensor in the endoplasmic reticulum (ER) together with the three downstream effector branches: inositol-requiring ser/thr protein kinase/endonuclease (IRE-1), PKR-like ER resident kinase (PERK) - activating transcription factor 6 (ATF-6). Through careful analysis of CHIKV - SINV infections in cell culture we found that the former selectively activates ATF-6 - IRE-1 branches of UPR - suppresses the PERK pathway. By separately expressing each of the CHIKV proteins as GFP-fusion proteins, we found that non-structural protein 4 (nsP4), which is a RNA-dependent-RNA polymerase, suppresses the serine-51 phosphorylation of eukaryotic translation initiation factor, alpha subunit (eIF2?), which in turn regulates the PERK pathway. This study provides insight into a mechanism by which CHIKV replication responds to overcome the host UPR machinery.

ImprentaVirology Journal, v. 10, p. 36, 2013

DescritoresChikungunya virus - Arbovirus ; Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Protein synthesis ; Chikungunya virus - Proteins ; Chikungunya virus - RNA ; Chikungunya virus - Infectious diseases ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Epidemic

Data de Publicação:2013