HMGB1 and Zika virus infectious disease: Several proteins involved in immune response regulating signaling pathways were also significantly stimulated by ZIKV infection, which includes interferon signaling, PKR interferon induction and antiviral response, role of pattern recognition receptor in recognition (PRRR) of bacteria and virus, Th1 pathway, HMGB1, TREM1, IL-17, IL-8, IL-6, IL-15 signaling, etc. (Figure 5B).