GSE123835

Zika virus antagonizes interferon response in patients and disrupts RIG-I-MAVS interaction through its CARD-TM domains

Submitted by zhiyong shen (Sun Yat-sen University, China) on Dec 14 2018

Platform: ngs – Illumina HiSeq 2500 (Homo sapiens)

Pubmed: 31183075

Summary The emerging threat to global health associated with the Zika virus (ZIKV) epidemics and its link to severe complications highlights a growing need to better understand the pathogenic mechanisms of ZIKV. Accumulating evidence for a critical role of type I interferon (IFN-I) in protecting hosts from ZIKV infection lies in the findings that ZIKV has evolved various strategies to subvert the host defense line by counteracting the early IFN induction or subsequent IFN signaling. Yet, mechanisms underlying the counter-IFN capability of ZIKV and its proteins, which might contribute to the well-recognized broad cellular tropisms and persistence of ZIKV, remain to be fully understood. In our current study, using RNA sequencing-based transcriptional profiling from the whole blood cells isolated from patients acutely infected by ZIKV, we found that transcriptional signatures of antiviral interferon-stimulated genes and innate immune sensors was absent in ZIKV-infected patients presents inactive as compared to healthy donors, suggesting that ZIKV might suppress the induction of IFN-I during the natural infection process in human. Furthermore, utilizing cellular or extracellular analysis of molecular interaction in a ZIKV NS4A-overexpression system, or in the context of actual ZIKV infection, we have identified that ZIKV NS4A directly binds MAVS and thereby interrupts RIG-I/MAVS interaction through its CARD-TM domains, leading to attenuated production of IFN-I. Taken together, these findings originated from patient studies have added new knowledge and molecular details to our understanding regarding how ZIKV mediates suppression of the IFN-I system and may provide new basis for future development of anti-ZIKV strategies.

6 Samples

ID	Title	Cell Type	Timepoint	Reported Virus	Virus Species
GSM3512219	XXD	peripheral blood		none	Uninfected
GSM3512220	CLL	peripheral blood		none	Uninfected
GSM3512221	YY	peripheral blood		none	Uninfected
GSM3512222	GXXB_1	peripheral blood	acute	Zika	Zika virus
GSM3512223	BXXB_1	peripheral blood	acute	Zika	Zika virus
GSM3512224	FXXB_1	peripheral blood	acute	Zika	Zika virus