Characterisation of the Semliki Forest Virus-host cell interactome reveals the viral capsid protein as an inhibitor of nonsense-mediated mRNA decay

Understanding the complex interactions between the viral and the host cell proteins is crucial for elucidating the mechanisms underlying successful virus replication strategies and for developing specific antiviral interventions. This project presents the first comprehensive protein-protein interaction map between the proteins of Semliki Forest Virus (SFV), a mosquito-borne member of the alphaviruses, and host cell proteins. We additionally overlay an SFV siRNA screen to assign pro- or antiviral functions to the interactors. Among the many identified cellular interactors of SFV proteins, there was an enrichment of factors involved in translation and nonsense-mediated mRNA decay (NMD). Validating these findings, we observed a general inhibition of NMD during SFV infection and demonstrated that transient expression of the SFV capsid protein was sufficient to inhibit NMD in cells.