Abstract
Type I interferon (IFN) serves as the first line of defense against invading pathogens. Inhibition of IFN-triggered signaling cascade by Zika virus (ZIKV) plays a critical role for ZIKV to evade antiviral responses from host cells. Here we demonstrate that ZIKV nonstructural proteins NS1, NS4B and NS2B3 inhibit the induction of IFN and downstream IFN-stimulated genes through diverse strategies. NS1 and NS4B of ZIKV inhibit IFNβ signaling at TANK-binding kinase 1 level, whereas NS2B-NS3 of ZIKV impairs JAK–STAT signaling pathway by degrading Jak1 and reduces virus-induced apoptotic cell death. Furthermore, co-operation of NS1, NS4B and NS2B3 further enhances viral infection by blocking IFN-induced autophagic degradation of NS2B3. Hence, our study reveals a novel antagonistic system employing multiple ZIKV nonstructural proteins in restricting the innate antiviral responses.
Highlights
Zika virus (ZIKV), an arbovirus belonging to the Flaviviridae family, was initially isolated from a rhesus monkey in Uganda as early as 1947 [1]
Overexpression of NS1 or NS4B alone but not NS2B3 inhibited cytoplasmic poly (I:C), poly as well as Sendai virus (SeV)-induced IFNβ reporter activation in 293T cells (Figure 1d–f). These results suggest that NS1 and NS4B of ZIKV may evade antiviral immunity by directly blocking type I IFN production
Many studies have reported IFN-stimulated genes (ISGs) such as IFITM family can inhibit the replication of ZIKV [17], little is known about the relationship between host IFN system and ZIKV replication
Summary
Zika virus (ZIKV), an arbovirus belonging to the Flaviviridae family, was initially isolated from a rhesus monkey in Uganda as early as 1947 [1]. ZIKV infection was previously thought to be asymptomatic, or to cause a mild, flu-like illness [2]. ZIKV caught people’s attention during the current wide-spread epidemic in the south Pacific, and south and central America with millions of people infected [3, 4]. As an early response to viral infection, type I interferon (IFN) produced by mammalian cells exerts antiviral activity [11]. Activation of IFN signaling initiates from the recognition of pathogen-associated molecular patterns by different pattern recognition receptors [12]. RIG-I-like receptors (RLRs), which recognize cytosolic viral RNA [13], have emerged as critical sensors for RNA viruses, including ZIKV [14]. The binding of viral RNA triggers conformation changes of RIG-I that exposes its CARD domains for
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
