Virus usurps alternative splicing to clear the decks for infection

Abstract

Since invasion, there will be a tug-of-war between host and virus to scramble cellular resources, for either restraining or facilitating infection. Alternative splicing (AS) is a conserved and critical mechanism of processing pre-mRNA into mRNAs to increase protein diversity in eukaryotes. Notably, this kind of post-transcriptional regulatory mechanism has gained appreciation since it is widely involved in virus infection. Here, we highlight the important roles of AS in regulating viral protein expression and how virus in turn hijacks AS to antagonize host immune response. This review will widen the understandings of host-virus interactions, be meaningful to innovatively elucidate viral pathogenesis, and provide novel targets for developing antiviral drugs in the future.

Keywords: Alternative splicing; Immune evasion; Viral protein expression; Virus infection.

Fig. 1

Virus manipulates the splicing of specific checkpoints in innate immune pathways to evade antiviral defense. STING-β negatively regulates the signal transduction through inhibiting cGAMP-STING and STING-TBK1 interactions and facilitates VSV-GFP and HSV-GFP replication. MRP similarly promotes SeV and VSV propagation through blocking STING-TBK1 interaction to inhibit IFN-I response. TBK1s binds to RIG-I to inhibit the interaction between RIG-I and MAVS upon SeV infection. TBK1s targets RIG-I to inhibit interaction between RIG-I and MAVS upon SeV infection. In SVCV-infected epithelioma papulosum cyprini cells, TBK1_tv1, TBK1_tv2, and TBK1-tv3 competitively associate with TBK1 and IRF3 to inhibit the formation of TBK1-IRF3 complex. And TBK1-tv3 additionally promotes the degradation of TBK1 and IRF3 through the ubiquitin–proteasome pathway and the lysosomal pathway, respectively. EBV SM protein upregulates the expression of STAT1β to exert negative effect on IFN response. HSV-1 and IAV creates a pro-viral state in infected cells by promoting the production of MxA isoforms