Insulin receptor isoform b is an essential factor for the entry of spring viremia of carp virus

Spring viraemia of carp virus (SVCV) causes the infectious and haemorrhagic disease spring viraemia of carp in cyprinids. Receptors determine the initiation of viral infection. However, the SVCV receptor remains unknown. The envelop glycoproteins (G proteins) of rhabdoviruses play a crucial role in viral entry. In this study, using immunoprecipitation followed by mass spectrometry, insulin receptor isoform b (Insrb) was found to interact with the SVCV G protein. Immunoprecipitation and immunofluorescence assays further confirmed that Insrb interacted with the SVCV G protein at the cell membrane. SVCV infection promoted Insrb expression both in vitro and in vivo. Insrb overexpression enhanced SVCV infection, whereas Insrb knockdown by siRNAs induced a marked reduction in the entry of SVCV into host cells. Treatment with the Insrb inhibitor NVP-ADW742 or Insrb antibodies effectively blocked SVCV infection. Moreover, in vivo experiments revealed that NVP-ADW742 provided protection to common carp against SVCV infection. The results of this study demonstrated that Insrb is an essential factor for SVCV cellular entry. These findings not only deepen our understanding of the cell entry mechanism of SVCV but also provide a promising therapeutic target against viral infection.