β-arrestins and G protein-coupled receptor kinases in viral entry: A graphical review

Viruses rely on host-cell machinery in order to invade host cells and carry out a successful infection. G-protein coupled receptor (GPCR)-mediated signaling pathways are master regulators of cellular physiological processing and are an attractive target for viruses to rewire cells during infection. In particular, the GPCR-associated scaffolding proteins beta-arrestins and GPCR signaling effectors G-protein receptor kinases (GRKs) have been identified as key cellular factors that mediate viral entry and orchestrate signaling pathways that reprogram cells for viral replication. Interestingly, a broad range of viruses have been identified to activate and/or require GPCR-mediated pathways for infection, including polyomaviruses, flaviviruses, influenza virus, and SARS-CoV-2, demonstrating that these viruses may have conserved mechanisms of host-cell invasion. Thus, GPCR-mediated pathways highlight an attractive target for the development of broad antiviral therapies.

Automated summary

Viruses exploit GPCR-mediated signaling pathways to invade host cells and reprogram cellular processes for viral replication. Beta-arrestins and GRKs, as crucial cellular factors, play a major role in viral entry and signaling pathway reprogramming. Various viruses, including polyomaviruses, flaviviruses, influenza virus, and SARS-CoV-2, activate or rely on GPCR-mediated pathways, suggesting the conservation of host-cell invasion mechanisms. Therefore, targeting GPCR-mediated pathways holds promise for the development of broad antiviral therapies.