SIAIS-Fudan Collaboration Reports New Progress on Zika Virus

ON2018-02-26TAG: ShanghaiTech UniversityCATEGORY: Published Research

Nature Microbiology recently made available as an Advance Online Publication the research findings of a collaboration between SIAIS Research Associate Professor Liu Jia from the Laboratory of ADC Chemistry and Professor Xu Jianqin from Fudan University Shanghai Public Health Clinical Center on new progress on Zika virus, elucidating the role of AXL in promoting Zika virus (ZIKV) infection.

ZIKV belongs to the flavivirus virus family and was discovered in the Zika forest in Uganda, Africa in 1947. There were very few early cases of ZIKV infection reporting infection-related human diseases, however, the ZIKV outbreak in South America has been shown to be associated with microcephaly in newborns and Guillain-Barré syndrome in adults. Despite studies showing the causal link between ZIKV infection and fetal birth defects, the mechanisms underlying ZIKV infection, especially its entry pathway, remain largely unknown. Among the others, the role of AXL during ZIKV infection has been controversial thus far. AXL belongs to TAM (Tyro3, AXL and Mertk) receptor tyrosine kinase. Several studies have suggested AXL as the entry receptor for Zika virus, and have shown that blocking AXL using antibodies, siRNA or genetic ablation can protect cells from ZIKV infection. However, conflicting studies suggest against the role of AXL as ZIKV entry receptor and have demonstrated in in vitro and in vivo studies that ZIKV infection can be AXL-independent.

In their study, Dr. Liu Jia and collaborator studied ZIKV infection in human astrocytes. They found that although targeted gene disruption of AXL could prevent ZIKV infection in human astrocytes, it did not block virus entry. This indicated that AXL did not function as the entry receptor of ZIKV but might instead promote ZIKV infection via alternative mechanisms. Further experiments elucidated that AXL promoted ZIKV infection by antagonizing type I interferon (IFN) signaling. Additionally, this study has illustrated the important role of SOCS1 in regulating type I IFN.

Research Assistant Professor Yang Yifeng from ShanghaiTech University and Graduate student Chen Jian from Fudan University are co-first authors of this study. Research Associate Professor Liu Jia from ShanghaiTech University and Professors Xu Jianqing and Zhang Xiaoyan from Fudan University are co-corresponding authors. National Natural Science Foundation of China and ShanghaiTech University provided financial support to this study.

Read More: https://www.nature.com/articles/s41564-017-0092-4

Note:a. AXL antagonizes type I IFN signaling during ZIKV infection. b. SOCS1 played a critical role in AXL-mediated regulation of type I IFN signaling.