m ⁶ A RNA methylation modulates Zika virus infection by regulating serine proteases in <i>Aedes albopictus</i>

Mosquito-borne viruses such as Zika virus pose a major threat to global public health. Successful transmission of these viruses depends not only on infection in humans, but also on their ability to replicate efficiently inside mosquito vectors. Chemical modifications of RNA, collectively known as epitranscriptomic marks, have recently emerged as important regulators of gene expression and virus-host interactions. Among these, N ⁶ -methyladenosine (m ⁶ A) is the most abundant internal RNA modification in eukaryotic cells. While m ⁶ A has been extensively studied in mammalian systems, its role in mosquito antiviral responses remains poorly understood. In this study, we investigated how m ⁶ A RNA methylation influences Zika virus infection in mosquito cells derived from <i>Aedes albopictus</i> . We found that reducing m ⁶ A levels enhances viral replication, indicating that this RNA modification restricts infection in mosquito cells. Notably, Zika virus RNA itself does not contain detectable m ⁶ A modifications. Instead, m ⁶ A regulates the expression of specific mosquito genes, including a group of serine proteases that influence viral replication. Pharmacological inhibition of these proteases significantly impaired virus growth, identifying them as key downstream effectors. Our findings reveal an antiviral role for m ⁶ A in mosquito cells and uncover a previously unrecognized epitranscriptomic pathway that shapes mosquito-virus interactions. Understanding how RNA modifications regulate arbovirus infection in vectors may open new avenues for strategies aimed at limiting virus transmission.