Chinese sacbrood virus mediates m6A modification to target and suppress the expression of hemolymph maintenance gene AF9, exacerbating bee infections

The Chinese sacbrood virus (CSBV) poses a serious threat to the health of <i>Apis cerana</i> colonies, yet its specific pathogenic mechanism remains unclear. This study shows that infection with CSBV can enhance overall m6A modification levels in <i>Apis cerana</i> larvae and suppress the expression of <i>AF9</i> by promoting targeting of AcMETTL3, thereby inhibiting the innate immune response and exacerbating CSBV infection. Further analyses indicated that <i>AF9</i> functions similarly as the mammalian homologous gene <i>MLLT3</i> by maintaining normal functions of hemolymph. Moreover, <i>AF9</i> can also significantly inhibit infections by common <i>Apis mellifera</i> viruses. In summary, a new mechanism is detailed here by which CSBV escapes the host's innate immune response by enhancing m6A modification to target and suppress the immune response gene <i>AF9</i>. This study also provides new insights into the mechanisms by which bee viruses inhibit host immune responses and suggests that <i>AF9</i> may serve as a potential new broad-spectrum antiviral target in bees.