Zika virus and host innate immunity: mechanisms of activation and evasion
TL;DR
This Review summarizes current knowledge of how the innate immune system recognizes ZIKV and how the virus counteracts these responses, while highlighting unresolved questions and potential therapeutic targets.
Abstract
Zika virus (ZIKV) is an Orthoflavivirus that poses a significant public health threat due to its unique capacity to cause congenital malformations, neurological disorders, and reproductive complications. Upon infection, host cells sense viral RNA and danger signals through pattern recognition receptors, including Toll-like receptors, RIG-I-like receptors, inflammasomes and the cGAS-STING pathway, leading to the production of type I interferons and the subsequent expression of interferon-stimulated genes. Additional intrinsic restriction mechanisms, such as apoptosis, autophagy, RNA interference, stress granules, and nonsense-mediated mRNA decay, further limit viral replication. In response, ZIKV has evolved coordinated immune evasion strategies whereby multiple viral proteins target key signaling molecules—including RIG-I, MDA5, TBK1, IRF3, and STAT1/2—to subvert host antiviral defenses and promote viral persistence. This Review summarizes current knowledge of how the innate immune system recognizes ZIKV and how the virus counteracts these responses, while highlighting unresolved questions and potential therapeutic targets.