Research Projects

Influenza A virus (IAV) is a significant global health and economic threat, causing seasonal epidemics and recurring pandemics. Current antivirals are ineffective against IAV due to resistance through mutations in viral genes. A promising approach of host-directed therapy has gained attention in the scientific community. The major vault protein (MVP), a key component of the vault complex, has been identified as a key determinant of IAV infection. MVP plays a critical role in immune response to infections by HIV, HSV, HCV, and IAV. However, its role in IAV infection at the cellular level has not been thoroughly investigated. To investigate the role of MVP in IAV infection, researchers depleted MVP using siRNAs targeting different regions of the gene in a lung epithelial cell line (A549) and infected the cells with IAV X-31 strain (H3N). They observed an 86-94% decrease in IAV infection in MVP-depleted cells compared to the negative control. The researchers plan to investigate the underlying mechanisms of MVP-mediated IAV entry using high-content, confocal, super-resolution microscopy, cell biology, and biochemical techniques. They will employ siRNA/shRNA-mediated knockdown and CRISPR/Cas9-driven knockout approaches to interrogate MVP's functions in A549 cells. Additionally, they will perform a high-throughput RNAi screen to identify potential MVP interactors. The results are expected to provide new insights into MVP and its interacting proteins' roles in supporting IAV entry, potentially leading to new targets for antiviral development.