Chikungunya Virus and Zika Virus, Two Different Viruses Examined with a Common Aim: Role of Pattern Recognition Receptors on the Inflammatory Response

López, Juan F.; Velilla, Paula A.; Urcuqui-Inchima, Silvio

doi:10.1089/jir.2019.0058

Cited by 13 publications

(11 citation statements)

References 127 publications

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“…Although antiviral properties of IL27 contribute to the control of CHIKV replication, its persistent or unregulated production could have important implications in the immunopathogenesis of CHIKF. Acute and chronic phases of CHIKF have an important immunopathological compound (Revised in ( Valdés-López et al, 2019 )). Here, we showed that IL27 promotes a protective antiviral state in MDMs to control CHIKV replication.…”

Section: Discussionmentioning

confidence: 99%

“…CHIKF is associated with the development of immunopathology linked to high levels of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNFα), Interleukin (IL) 1β (IL1β), IL6, IL12p70, and IL15, both CC- and CXC-chemokines (CCL2, CCL3, CCL5, CCL8, CXCL9, CXCL10, and CXCL11), both in CHIKV-infected patients and in vitro culture ( Wauquier et al, 2011 ; Dupuis-Maguiraga et al, 2012 ; Gasque et al, 2015 ; Valdés-López et al, 2019 ). Among the cytokines/chemokines, IL1β, IL6, CCL5, and CCL8 are correlated with the severity of CHIKF, while others, including IL1Ra, IL12p70, IL16, IL17, IL18, CCL2, and CXCL10, are correlated with high CHIKV loads ( Chow et al, 2011 ; Dupuis-Maguiraga et al, 2012 ); Cavalcanti et al (2019) reported that serum levels of IL27 were higher in patients with chronic CHIKF than in the ones with acute or subacute disease.…”

Section: Introductionmentioning

confidence: 99%

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Synergistic Effects of Toll-Like Receptor 1/2 and Toll-Like Receptor 3 Signaling Triggering Interleukin 27 Gene Expression in Chikungunya Virus-Infected Macrophages

Valdés-López

Fernández

Urcuqui-Inchima

2022

Front. Cell Dev. Biol.

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Chikungunya virus (CHIKV) is the etiological agent of chikungunya fever (CHIKF), a self-limiting disease characterized by myalgia and severe acute or chronic arthralgia. CHIKF is associated with immunopathology and high levels of pro-inflammatory factors. CHIKV is known to have a wide range of tropism in human cell types, including keratinocytes, fibroblasts, endothelial cells, monocytes, and macrophages. Previously, we reported that CHIKV-infected monocytes-derived macrophages (MDMs) express high levels of interleukin 27 (IL27), a heterodimeric cytokine consisting of IL27p28 and EBI3 subunits, that triggers JAK-STAT signaling and promotes pro-inflammatory and antiviral response, in interferon (IFN)-independent manner. Based on the transcriptomic analysis, we now report that induction of IL27-dependent pro-inflammatory and antiviral response in CHIKV-infected MDMs relies on two signaling pathways: an early signal dependent on recognition of CHIKV-PAMPs by TLR1/2-MyD88 to activate NF-κB-complex that induces the expression of EBI3 mRNA; and second signaling dependent on the recognition of intermediates of CHIKV replication (such as dsRNA) by TLR3-TRIF, to activate IRF1 and the induction of IL27p28 mRNA expression. Both signaling pathways were required to produce a functional IL27 protein involved in the induction of ISGs, including antiviral proteins, cytokines, CC- and CXC- chemokines in an IFN-independent manner in MDMs. Furthermore, we reported that activation of TLR4 by LPS, both in human MDMs and murine BMDM, results in the induction of both subunits of IL27 that trigger strong IL27-dependent pro-inflammatory and antiviral response independent of IFNs signaling. Our findings are a significant contribution to the understanding of molecular and cellular mechanisms of CHIKV infection.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synergistic Effects of Toll-Like Receptor 1/2 and Toll-Like Receptor 3 Signaling Triggering Interleukin 27 Gene Expression in Chikungunya Virus-Infected Macrophages

Valdés-López

Fernández

Urcuqui-Inchima

2022

Front. Cell Dev. Biol.

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“…In the case of CHIKV, double stranded RNA (dsRNA) induce toll like receptor (TLR) 3, retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5), while single-stranded RNA (ssRNA) induce TLR-7 (49)(50)(51)(52). A signaling cascade is initiated which results in activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and interferon regulator factors (IRFs) inducing the transcription of interferons and pro-inflammatory cytokines (49,(52)(53)(54). See Figure 1 for more detail.…”

Section: Pathogenesis Innate Immunitymentioning

confidence: 99%

“…The produced type I interferons (IFN α/β) bind to receptors IFNAR1 and 2 (interferon receptor α/β) inducing phosphorylation of Janus kinase 1 (JAK1) and tyrosine kinase 2 (TYK2) which leads to assembly of interferon stimulated gene factor 3 (ISGF3) complex. ISGF3 binds to interferon stimulated genes (ISGs) resulting in gene expression of IFNs ( 52 , 53 , 55 , 56 ). As expected, CHIKV developed mechanisms to counteract the host immune response.…”

Section: Pathogenesismentioning

confidence: 99%

“…As expected, CHIKV developed mechanisms to counteract the host immune response. CHIKV inhibits IFN signaling with its own nsP2 by blocking the JAK/STAT (signal transducer and activator of transcription) signaling pathway ( 53 , 57 ). Also, CHIKV nsP2 inhibits RNA polymerase II by inducing the degradation of its catalytic subunit RpB1, blocking the expression of cellular genes ( 53 , 58 , 59 ).…”

Section: Pathogenesismentioning

confidence: 99%

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Human Genetic Host Factors and Its Role in the Pathogenesis of Chikungunya Virus Infection

et al. 2022

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Chikungunya virus (CHIKV) is an alphavirus from the Togaviridae family that causes acute arthropathy in humans. It is an arthropod-borne virus transmitted initially by the Aedes (Ae) aegypti and after 2006's epidemic in La Reunion by Ae albopictus due to an adaptive mutation of alanine for valine in the position 226 of the E1 glycoprotein genome (A226V). The first isolated cases of CHIKV were reported in Tanzania, however since its arrival to the Western Hemisphere in 2013, the infection became a pandemic. After a mosquito bite from an infected viremic patient the virus replicates eliciting viremia, fever, rash, myalgia, arthralgia, and arthritis. After the acute phase, CHIKV infection can progress to a chronic stage where rheumatic symptoms can last for several months to years. Although there is a great number of studies on the pathogenesis of CHIKV infection not only in humans but also in animal models, there still gaps in the proper understanding of the disease. To this date, it is unknown why a percentage of patients do not develop clinical symptoms despite having been exposed to the virus and developing an adaptive immune response. Also, controversy stills exist on the pathogenesis of chronic joint symptoms. It is known that host immune response to an infectious disease is reflected on patient's symptoms. At the same time, it is now well-established that host genetic variation is an important component of the varied onset, severity, and outcome of infectious disease. It is essential to understand the interaction between the aetiological agent and the host to know the chronic sequelae of the disease. The present review summarizes the current findings on human host genetics and its relationship with immune response in CHIKV infection.

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Protective Effects of Caffeine on Chikungunya and Zika Virus Infections: An in Vitro and in Silico Study

de Jesús López Medina,

Tamayo‐Molina,

Valdés‐López

et al. 2023

Chemistry & Biodiversity

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Infection by viruses Chikungunya (CHIKV) and Zika (ZIKV) continue to be serious problems in tropical and subtropical areas of the world. Here, we evaluated the antiviral and virucidal activity of caffeine against CHIKV and ZIKV in Vero, A549, and Huh‐7 cell lines. Results showed that caffeine displays antiviral properties against both viruses. By pre‐and post‐infection treatment, caffeine significantly inhibited CHIKV and ZIKV replication in a dose‐dependent manner. Furthermore, caffeine showed a virucidal effect against ZIKV. Molecular docking suggests the possible binding of caffeine with envelope protein and RNA‐dependent RNA polymerase of CHIKV and ZIKV. This is the first study that showed an antiviral effect of caffeine against CHIKV and ZIKV. Although further studies are needed to better understand the mechanism of caffeine‐mediated repression of viral replication, caffeine appears to be a promising compound that could be used for in vivo studies, perhaps in synergy with other compounds present in daily beverages.

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Chikungunya Virus and Zika Virus, Two Different Viruses Examined with a Common Aim: Role of Pattern Recognition Receptors on the Inflammatory Response

Cited by 13 publications

References 127 publications

Synergistic Effects of Toll-Like Receptor 1/2 and Toll-Like Receptor 3 Signaling Triggering Interleukin 27 Gene Expression in Chikungunya Virus-Infected Macrophages

Synergistic Effects of Toll-Like Receptor 1/2 and Toll-Like Receptor 3 Signaling Triggering Interleukin 27 Gene Expression in Chikungunya Virus-Infected Macrophages

Human Genetic Host Factors and Its Role in the Pathogenesis of Chikungunya Virus Infection

Protective Effects of Caffeine on Chikungunya and Zika Virus Infections: An in Vitro and in Silico Study

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