Interferon-Induced Spermidine-Spermine Acetyltransferase and Polyamine Depletion Restrict Zika and Chikungunya Viruses

Polyamines are small, positively charged molecules derived from ornithine and synthesized through an intricately regulated enzymatic pathway. Within cells, they are abundant and play several roles in diverse processes. We find that polyamines are required for the life cycle of the RNA viruses chikungunya virus (CHIKV) and Zika virus (ZIKV). Depletion of spermidine and spermine via type I interferon signaling-mediated induction of spermidine/spermine N1-acetyltransferase (SAT1), a key catabolic enzyme in the polyamine pathway, restricts CHIKV and ZIKV replication. Polyamine depletion restricts these viruses in vitro and in vivo, due to impairment of viral translation and RNA replication. The restriction is released by exogenous replenishment of polyamines, further supporting a role for these molecules in virus replication. Thus, SAT1 and, more broadly, polyamine depletion restrict viral replication and suggest promising avenues for antiviral therapies. [Display omitted] •Type I interferon induces SAT1, a catabolic enzyme in the host polyamine pathway•SAT1 depletes spermidine and spermine to restrict RNA virus replication•Chikungunya and Zika viruses require polyamines for transcription and translation•Polyamine depletion in vivo limits RNA virus replication Mounce et al. demonstrate that signaling through type I interferon induces a catabolic enzyme in the host polyamine pathway, which depletes spermidine and spermine to restrict chikungunya and Zika virus replication. Polyamines were found to be crucial for viral infection in vivo, suggesting a therapeutic avenue for virus control.