Zika virus evades interferon-mediated antiviral response through the co-operation of multiple nonstructural proteins in vitro

Wu, Yiming; Liu, Qingxiang; Zhou, Jie; Xie, Weidong; Chen, Cheng; Wang, Zefang; Yang, Haitao; Cui, Jun

doi:10.1038/celldisc.2017.6

Cited by 173 publications

(216 citation statements)

References 44 publications

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“…(80, 81) Additionally, flavivirus non-structural (NS) proteins and subgenomic flavivirus RNA (sfRNA) can directly interfere with host antiviral signaling pathways to suppress immunity. (82–88) For ZIKV, the viral proteins NS1, NS2A, and NS4B have been demonstrated to antagonize the innate immune response at the level of IKKε/TBK1 (Inhibitor of kappa B kinase epsilon/TANK-binding kinase 1) activation(87, 88); whereas, NS5 has been shown to act downstream by binding IRF3 (interferon regulatory factor 3, Fig. 4).…”

Section: How Zikv Escapes the Immune Response And Emerging Viruses Wimentioning

confidence: 99%

“…(82) ZIKV further inhibits innate immunity via disruption of the JAK/STAT (janus kinase/signal transducer and activator of transcription) signaling cascade that is required to direct the expression of any antiviral genes induced by interferon. This antagonism is mediated by the viral protease NS2B/3-stimulated degradation of JAK1(88) while NS5 binds and degrades human STAT2. (84, 86) Other mechanisms of flavivirus innate immune antagonism include induction of major histocompatibility expression (MHC-I) on the surface of infected cells to evade natural killer cell-mediated lysis.…”

Section: How Zikv Escapes the Immune Response And Emerging Viruses Wimentioning

confidence: 99%

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Zika virus and the nonmicrocephalic fetus: why we should still worry

Walker

Little²,

Roby

et al. 2019

American Journal of Obstetrics and Gynecology

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Zika virus (ZIKV) is a mosquito-transmitted flavivirus and was first linked to congenital microcephaly due to a large outbreak in Northeastern Brazil. Although the ZIKV epidemic is now in decline, pregnancies in large parts of the Americas remain at risk due to ongoing transmission and the potential for new outbreaks. This review presents why Zika virus is still a complex and worrisome public health problem with an expanding spectrum of birth defects and why ZIKV and related viruses may evade the immune response to injure the fetus. Recent reports indicate that the spectrum of fetal brain and other anomalies associated with ZIKV exposure is broader and more complex than microcephaly alone and includes subtle fetal brain and ocular injuries; thus, the ability to prenatally diagnose fetal injury associated with ZIKV infection remains limited. New studies indicate that ZIKV imparts disproportionate effects on fetal growth with an unusual femur-sparing profile, potentially providing a new approach to identify viral injury to the fetus. Studies to determine the limitations of prenatal and postnatal testing for detection of ZIKV-associated birth defects and long-term neurocognitive deficits are needed to better guide counseling for women with a possible infectious exposure. It is also imperative that we investigate why ZIKV is so adept at infecting the placenta and the fetal brain to better predict other viruses with similar capabilities that may give rise to new epidemics. The efficiency with which ZIKV evades the early immune response to enable infection of the mother, placenta and fetus is likely critical for understanding why the infection may either be fulminant or limited. Furthermore, studies suggest that several emerging and related viruses may also cause birth defects, including West Nile virus, which is endemic in many parts of the United States. With mosquito-borne diseases increasing worldwide, there remains an urgent need to better understand the pathogenesis of ZIKV and related viruses to protect pregnancies and child health.

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Section: How Zikv Escapes the Immune Response And Emerging Viruses Wimentioning

confidence: 99%

Section: How Zikv Escapes the Immune Response And Emerging Viruses Wimentioning

confidence: 99%

Zika virus and the nonmicrocephalic fetus: why we should still worry

Walker

Little²,

Roby

et al. 2019

American Journal of Obstetrics and Gynecology

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“…Type I interferon (IFN) response serves as the first line of defense to combat viral infection (Schneider et al , ). Recently, we and other groups have demonstrated that ZIKV evolved several strategies to counter human IFN antiviral response (Fernandez‐Garcia et al , ; Grant et al , ; Kumar et al , ; Wu et al , ; Xia et al , ). The IFN‐antagonistic strategies can be mainly divided into two types (Fernandez‐Garcia et al , ): The first strategy employed by ZIKV is to reduce and delay the activation of IFN production.…”

Section: Introductionmentioning

confidence: 99%

“…The IFN‐antagonistic strategies can be mainly divided into two types (Fernandez‐Garcia et al , ): The first strategy employed by ZIKV is to reduce and delay the activation of IFN production. For example, we recently reported that NS1 and NS4B of ZIKV blocked virus‐mediated IFN signaling by targeting TBK1 (Wu et al , ). Xia et al showed the similar result of NS1 and found that residue 188 is critical for the inhibition of IFN (Xia et al , ).…”

Section: Introductionmentioning

confidence: 99%

Zika virus elicits inflammation to evade antiviral response by cleaving cGAS via NS 1‐caspase‐1 axis

et al. 2018

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Viral infection triggers host innate immune responses, which primarily include the activation of type I interferon (IFN) signaling and inflammasomes. Here, we report that Zika virus (ZIKV) infection triggers NLRP3 inflammasome activation, which is further enhanced by viral non-structural protein NS1 to benefit its replication. NS1 recruits the host deubiquitinase USP8 to cleave K11-linked poly-ubiquitin chains from caspase-1 at Lys134, thus inhibiting the proteasomal degradation of caspase-1. The enhanced stabilization of caspase-1 by NS1 promotes the cleavage of cGAS, which recognizes mitochondrial DNA release and initiates type I IFN signaling during ZIKV infection. NLRP3 deficiency increases type I IFN production and strengthens host resistance to ZIKV and Taken together, our work unravels a novel antagonistic mechanism employed by ZIKV to suppress host immune response by manipulating the interplay between inflammasome and type I IFN signaling, which might guide the rational design of therapeutics in the future.

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“…Another study showed that Zika virus infection impairs the induction of type I IFNs and that the viral NS5 protein mediates the degradation of STATs in the proteasome (66). Zika virus nonstructural proteins NS1, NS4B, and NS2B3 have been found to inhibit the induction of IFN downstream ISGs through several pathways, including inhibition of IFN-␤ and JAK STAT signaling (67).…”

Section: Zika Virus Escapes Nk Cell Detectionmentioning

confidence: 99%

Zika Virus Escapes NK Cell Detection by Upregulating Major Histocompatibility Complex Class I Molecules

Glasner

Oiknine‐Djian

Weisblum

et al. 2017

J Virol

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NK cells are innate lymphocytes that participate in many immune processes encompassing cancer, bacterial and fungal infection, autoimmunity, and even pregnancy and that specialize in antiviral defense. NK cells express inhibitory and activating receptors and kill their targets when activating signals overpower inhibitory signals. The NK cell inhibitory receptors include a uniquely diverse array of proteins named killer cell immunoglobulin-like receptors (KIRs), the CD94 family, and the leukocyte immunoglobulin-like receptor (LIR) family. The NK cell inhibitory receptors recognize mostly major histocompatibility complex (MHC) class I (MHC-I) proteins. Zika virus has recently emerged as a major threat due to its association with birth defects and its pandemic potential. How Zika virus interacts with the immune system, and especially with NK cells, is unclear. Here we show that Zika virus infection is barely sensed by NK cells, since little or no increase in the expression of activating NK cell ligands was observed following Zika infection. In contrast, we demonstrate that Zika virus infection leads to the upregulation of MHC class I proteins and consequently to the inhibition of NK cell killing. Mechanistically, we show that MHC class I proteins are upregulated via the RIGI-IRF3 pathway and that this upregulation is mediated via beta interferon (IFN-␤). Potentially, countering MHC class I upregulation during Zika virus infection could be used as a prophylactic treatment against Zika virus.IMPORTANCE NK cells are innate lymphocytes that recognize and eliminate various pathogens and are known mostly for their role in controlling viral infections. NK cells express inhibitory and activating receptors, and they kill or spare their targets based on the integration of inhibitory and activating signals. Zika virus has recently emerged as a major threat to humans due to its pandemic potential and its association with birth defects. The role of NK cells in Zika virus infection is largely unknown. Here we demonstrate that Zika virus infection is almost undetected by NK cells, as evidenced by the fact that the expression of activating ligands for NK cells is not induced following Zika infection. We identified a mechanism whereby Zika virus sensing via the RIGI-IRF3 pathway resulted in IFN-␤-mediated upregulation of MHC-I molecules and inhibition of NK cell activity. Countering MHC class I upregulation and boosting NK cell activity may be employed as prophylactic measures to combat Zika virus infection.KEYWORDS Zika virus, MHC class I, NK cells, NK escape mechanisms N K cells are lymphocytes belonging to the innate immune system. NK cells participate in many immunological activities, from killing cancerous cells (1-7) and fighting bacteria (8-10) and fungi (11) to playing roles in allergy (12) and graft-versushost disease (13). NK cells also play roles in autoimmunity (14-18) and pregnancy (19).

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Zika virus evades interferon-mediated antiviral response through the co-operation of multiple nonstructural proteins in vitro

Cited by 173 publications

References 44 publications

Zika virus and the nonmicrocephalic fetus: why we should still worry

Zika virus and the nonmicrocephalic fetus: why we should still worry

Zika virus elicits inflammation to evade antiviral response by cleaving cGAS via NS 1‐caspase‐1 axis

Zika Virus Escapes NK Cell Detection by Upregulating Major Histocompatibility Complex Class I Molecules

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