Autophagy Contributes to Host Immunity and Protection against Zika Virus Infection via Type I IFN Signaling.

Yuyi Huang,Shuhui Meng,Gen Lu,Zhuohang Chen,Ting Pan,Yujie Wang,Xuefeng Li,Haifan Kong

doi:10.1155/2020/9527147

Abstract

Recent studies have indicated that the Zika virus (ZIKV) has a significant impact on the fetal brain, and autophagy is contributing to host immune response and defense against virus infection. Here, we demonstrate that ZIKV infection triggered increased LC3 punctuation in mouse monocyte-macrophage cell line (RAW264.7), mouse microglial cell line (BV2), and hindbrain tissues, proving the occurrence of autophagy both in vitro and in vivo. Interestingly, manual intervention of autophagy, like deficiency inhibited by 3-MA, can reduce viral clearance in RAW264.7 cells upon ZIKV infection. Besides, specific siRNA strategy confirmed that autophagy can be activated through Atg7-Atg5 and type I IFN signaling pathway upon ZIKV infection, while knocking down of Atg7 and Atg5 effectively decreased the ZIKV clearance in phagocytes. Furthermore, we analyzed that type I IFN signaling could contribute to autophagic clearance of invaded ZIKV in phagocytes. Taken together, our findings demonstrate that ZIKV-induced autophagy is favorable to activate host immunity, particularly through type I IFN signaling, which participates in host protection and defense against ZIKV infection.

Highlights

Zika virus (ZIKV) is a flavivirus that was first detected in Uganda and named after the Zika forest
When mice were born the first day, we detected the viral burden in the brain of the suckling mouse and found that all neonatal mice were infected with different ZIKV stains (Figure 1(a))
Our results demonstrate that maternal ZIKV infection could induce immune cell accumulation in the brain of filial generation, we are not sure whether these are resident or infiltrating cells

Summary

Introduction

Zika virus (ZIKV) is a flavivirus that was first detected in Uganda and named after the Zika forest. It was first discovered in the rhesus monkey in 1947 and in humans in 1952 [1, 2]. ZIKV has been detected in the urine, serum, amniotic fluid of pregnant women, and brain of fetuses with microcephaly [11, 12]. It is confirmed that after the outbreak of the ZIKV epidemic, multiple cases of febrile rash in Mediators of Inflammation pregnant women associated with ZIKV were reported, which indicated that the virus can cross the placental barrier and infect the newborn brain tissue [13]

Methods

Results

Conclusion