Proteomics Profiling of Chikungunya-Infected Aedes albopictus C6/36 Cells Reveal Important Mosquito Cell Factors in Virus Replication.

Chikungunya virus (CHIKV) is the only causative agent of CHIKV fever with persistent arthralgia, and in some cases may lead to neurological complications which can be highly fatal, therefore it poses severe health issues in many parts of the world. CHIKV transmission can be mediated via the Aedes albopictus mosquito; however, very little is currently known about the involvement of mosquito cellular factors during CHIKV-infection within the mosquito cells. Unravelling the neglected aspects of mosquito proteome changes in CHIKV-infected mosquito cells may increase our understanding on the differences in the host factors between arthropod and mammalian cells for successful replication of CHIKV. In this study, the CHIKV-infected C6/36 cells with differential cellular proteins expression were profiled using two-dimensional gel electrophoresis (2DE) coupled with the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). 2DE analysis on CHIKV-infected C6/36 cells has shown 23 mosquito cellular proteins that are differentially regulated, and which are involved diverse biological pathways, such as protein folding and metabolic processes. Among those identified mosquito proteins, spermatogenesis-associated factor, enolase phosphatase e-1 and chaperonin-60kD have been found to regulate CHIKV infection. Furthermore, siRNA-mediated gene knockdown of these proteins has demonstrated the biological importance of these host proteins that mediate CHIKV infection. These findings have provided an insight to the importance of mosquito host factors in the replication of CHIKV, thus providing a potential channel for developing novel antiviral strategies against CHIKV transmission. Author Summary: Chikungunya virus (CHIKV), a re-emerging mosquito-borne virus, is the main cause of CHIKV fever, persistent arthralgia and serious neurological complications which can be highly fatal; therefore, it poses serious health threats worldwide. Unraveling the underappreciated aspects of mosquito cellular factors that contribute to the replication processes of CHIKV was performed using two-dimensional gel electrophoresis (2DE) coupled with the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The 2DE proteomics profiling of CHIKV-infected mosquito C6/36 cells has revealed twenty-three proteins that were differentially regulated upon CHIKV infection. These proteins are shown to be involved in diverse biological pathways and cellular processes. Notably, upon selected genes knockdown, spermatogenesis-associated factor, enolase phosphatase e-1 and chaperonin-60kD are found to be important during the replication processes of CHIKV. This study illustrates the importance of mosquito cellular factors in association with CHIKV infection in mosquito cells and reveals an interesting portal for developing novel antiviral strategies in CHIKV studies. [ABSTRACT FROM AUTHOR]