Recent studies present valid arguments for the worldwide epidemic threat of alphaviruses (among other arboviruses) that currently circulate endemically in particular regions. In addition to observing a general inhibition of NMD about 4 hours post infection, we also demonstrate that transient expression of the SFV capsid protein is sufficient to inhibit NMD in cells, suggesting that the massive production of capsid protein during the SFV reproduction cycle is responsible for NMD inhibition.Īs we live through the current SARS-COV2 pandemic, the world is reminded of the unpredictable nature of viral epidemics and the importance of studying potential emerging viral threats. Among the many identified cellular interactors of SFV proteins, the enrichment of factors involved in translation and nonsense-mediated mRNA decay (NMD) was striking, reflecting the virus’ hijacking of the translation machinery and indicating viral countermeasures for escaping NMD by inhibiting NMD at later time points during the infectious cycle. Here we present 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. 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. The positive-sense, single-stranded RNA alphaviruses pose a potential epidemic threat. None were identified as having a potential antiviral role (Threshold ≥ 1.3). SFV-ribosomal host protein interactors identified through a genome-wide fluorescence microscopy based siRNA screen as exhibiting potential proviral roles in SFV replication are additionally shown (turquoise borders, II ≤ 0.5). The host interactors were collected based on three independent biological replicates. Host-host PPI ascertained through STRING analysis are depicted with dotted pink lines. In these cases, the solid grey lines connect the grouped set of host proteins to the SFV proteins for which they were identified as interactors. Grey boxes reflect host proteins that were identified as interactors to more than one of the SFV proteins. SFV-host PPI are depicted with solid grey lines. SFV proteins are depicted in black circles and host proteins are displayed in smaller colour-coded circles according to the key. In total, 77 ribosomal host proteins are displayed. S3 Fig: A network visualisation of the SFV-ribosomal host protein interactome.
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