Zika Virus Proteins NS2A and NS4A Are Major Antagonists that Reduce IFN-�� Promoter Activity Induced by the MDA5/RIG-I Signaling Pathway

EVs Containing Host Restriction Factor IFITM3 Inhibited ZIKV Infection of Fetuses in Pregnant Mice through Trans-placenta Delivery

“…Moreover, ZIKV infection can inhibit type I IFN and downstream signaling, thus further suppressing endogenous IFITM expression. [38][39][40] Therefore, the IFITM3 presented on the surface of EVs is a plausible approach to elevate the IFITM3 in the fetus to combat ZIKV infection, as shown in the current study both in vitro and in vivo. Importantly, exosomal IFITM3 was transported through pregnant mice to their fetuses, concentrated in fetal organs, including brains, and reduced ZIKV loads of both the pregnant mice and the fetuses, demonstrating that EVs can package and effectively transport an exogenous antiviral protein across the placenta to fetuses, and control intrauterine viral infection.…”

ZIKV viral proteins and their roles in virus-host interactions

“…The precursor membrane (prM) protein is one of the structural proteins on the surface of the envelope of ZIKV particles, and plays an important role in the assembly and maturation of virus particles. The protein interacts with the E protein in the ER membrane, and then encapsulates the viral nucleocapsid to produce immature virus particles (Hasan et al, 2018;Nambala and Su, 2018). During the transport of immature virus particles to the Golgi apparatus, prM protects the E protein from premature fusion.…”

“…In addition to playing a direct role in the life cycle of ZIKV, recent studies indicate that NS2A is also involved in regulating the host innate immune response and has causal re-lations with neurological diseases. Xia et al have shown that NS2A can inhibit the IFN response by participating in the inhibition of TBK1 phosphorylation (Xia et al, 2018); Nguyen et al have revealed that NS2A can directly inhibit RIG-I and IRF3 to antagonize the RIG-I/MDA5 pathwaymediated production of interferon-β (IFN-β) (Ngueyen et al, 2019). Yoon et al found that NS2A can directly mediate the degradation of adhesion junction proteins, thereby destroying the neurogenesis of mammalian cortex, and similar phenomena were also observed in West Nile virus (WNV) and Japanese encephalitis virus (JEV) infections (Yoon et al, 2017).…”

“…Wu et al found that NS4B can combine with TBK1 to inhibit the production of type I interferon, which is also reported by Xia et al (Wu et al, 2017;Xia et al, 2018). Furthermore, NS4A blocks interferon regulatory factor 3 (IRF3) phosphorylation, thus preventing the production of type I IFN induced by the melanoma differentiation associated gene 5 (MDA5)/retinoic acid-inducible gene I (RIG-I) signaling pathway (Hu et al, 2019;Ma et al, 2018;Ngueyen et al, 2019;Xia et al, 2018). The research of Ma et al showed that NS4A combines with MAVS to hinder the interaction between mitochondrial antiviral signaling protein (MAVS) and RIG-I and thus reduces the induction of type I IFN, which is also supported by Hu et al (Hu et al, 2019;Ma et al, 2018).…”

Middle East Respiratory Syndrome Coronavirus-Encoded ORF8b Inhibits RIG-I-Like Receptors in a Differential Mechanism

“…Construction of expression plasmids for accessory genes of MERS-CoV and the host signaling molecules (RIG-I and IRF3) was described elsewhere [22,46]. RIG-I-1-228, consisting only of two N-terminal CARDs, and RIG-I-1-734, deficient of C-terminal regulatory domain (RD), were generated by PCR amplification and cloning into pcDNA3.1-Hygro-JY4-HAN-GS3 [55]. An IRF3-1-390-expressing plasmid was similarly generated.…”