Dynamics of Human and Viral RNA Methylation during ZIKA Virus Infection

Human infection with the flavivirus ZIKA (ZIKV) causes severe neurological, immunological, and developmental defects. Despite recent progress, the mechanisms by which ZIKV infection alters host transcriptional and translational programs remains unclear. Here, we report that ZIKV infection has profound effects on the topology and function of N6-adenosine methylation (m6A) of both viral and human RNAs. m6A and 2'-O-methylated nucleosides are abundant in ZIKV genomic RNA, and m6A-seq identified 12 m6A peaks spanning the full length of ZIKV RNA. m6A abundance in ZIKV RNA is controlled by the host methyltransferases METTL3 and METTL14 and the demethylase ALKBH5. Profiling of the m6A methylome of host mRNAs revealed that ZIKV infection alters the location of m6A in mRNAs, the methylation motifs, and the target genes modified by the methyltransferases. Our results identify a new mechanism by which ZIKV interacts with and alters the function of the host cell. Overall design: m6A-seq of virus genomic RNA and mRNA from human cells infected with virus.