Host-Pathogen Interactions:
To colonize within the host, influenza viruses hijack various host proteins, to facilitate different steps of its replication cycle. Host, on the other hand, also deploys several antiviral defense mechanisms to restrict virus propagation. During this tug-of-war, influenza virus RNPs interact with a plethora of host factors (both anti- and pro-viral) which determines the outcome of the virus life cycle.
1. RNP associated host kinases as critical regulator of virus replication
Proteins constituting viral RNPs, namely PB1, PB2, PA and NP, are known to get phosphorylation by host kinases. Phosphorylation of these viral proteins by the host Protein Kinase C (PKC) and Mitogen Activated Protein Kinase (MAPK) family of kinases regulate assembly, nuclear-cytoplasmic trafficking, and RNA synthesis activity of RNPs. We are interested in characterizing the complex network of interaction between viral RNPs with the host kinases and the precise mode of timely regulation of multiple host kinase activities, which should be critical for optimum multiplication of the virus within its host. Understanding this spatiotemporal dynamics of virus-host kinase interaction may help us identify novel small molecules perturbing the same and hence interfering with virus propagation.
NP -host kinase interactions achieved using in-cell Proximity ligation assay (PLA) indicated by Red Dots. After infecting the cells with Influenza virus, viral NP (green dots) interacts with the host kinase. Short oligo tagged antibodies targeted to NP and host kinase come in close proximity and amplify through rolling circle replication, resulting in red PLA dots. Quantification of the dots shows specific enrichment of the interaction than isotype control antibodies.
Publication details:
Dey S, Mondal A*. Unveiling the role of host kinases at different steps of influenza A virus life cycle. Journal of Virology. 2024 Jan 23;98(1): e0119223. doi: 10.1128/jvi.01192-23. Epub 2024 Jan 4. PMID: 38174932.
2. DEAD Box RNA Helicases: a double edged sword against Flu
DEAD box proteins constitute a major family of RNA helicases crucial for various host cell functions such as RNA metabolism and innate immune responses. Among them, DDX3X, DDX5, DDX17, and DDX21 have been reported to positively as well as negatively regulate the influenza virus life cycle through interaction with RNPs, although the precise molecular mechanisms are still elusive. Our research aims to characterize the molecular interaction between DDX3X and RNP components and elucidate its role in regulating viral RNA synthesis and virus propagation. We anticipate that these information will unravel the unexplored functions of Dead box helicases in modulating influenza and other RNA virus life cycle.
Human DEAD box RNA helicase 3X(DDX3X) acts as an antiviral host factor for Influenza B virus. It interacts with viral genomic RNA and downregulates viral RNA synthesis in a helicase dependent way. It also interacts with Nucleoprotein(NP) and upregulates host innate immune response.