Cytokines and Chemokines in Chikungunya Virus Infection: Protection or Induction of Pathology

Chirathaworn, Chintana; Chansaenroj, Jira; Poovorawan, Yong

doi:10.3390/pathogens9060415

Cited by 31 publications

(27 citation statements)

References 48 publications

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“…Chikungunya virus infection is known to cause severe musculoskeletal disorder, but the molecular mechanism involved in this process is not fully understood (Maek-A-Nantawat and Silachamroon, 2009). Observational studies in human subjects revealed that CHIKV infection elicits immune mechanisms similar to autoimmune diseases, which might explain the similarity between the arthritic phenomenon that occurred during the infection with rheumatoid arthritis (RA) (Chirathaworn et al, 2020). We categorize below the innate and the adaptive immune responses during CHIKV infection.…”

Section: Immunopathogenesismentioning

confidence: 99%

“…CHIKV uses this artifice to hijack host defense and be able to infect target cells on epithelial tissue. On the other hand, after this initial step, CHIKV infection induces an exacerbated local innate immunity (Tanabe et al, 2018;Cook et al, 2019;Foresto et al, 2019;Maucourant et al, 2019;Hiroki et al, 2020) in which macrophages (MØ), natural killer cells (NK), neutrophils, DCs, basophils, and eosinophils are recruited to the site of infection as a result of the release of several chemoattractant molecules by the infected cells (Ng et al, 2009;Waymouth et al, 2013;Chirathaworn et al, 2020). Monocyte chemoattractant protein-1 (MCP-1), granulocyte colony-stimulating factor (G-CSF), and granulocytemacrophage colony-stimulating factor (GM-CSF) are the main chemokines released by these cells (Couderc et al, 2008;Ng et al, 2009).…”

Section: Innate Immune Systemmentioning

confidence: 99%

See 1 more Smart Citation

Overview on Chikungunya Virus Infection: From Epidemiology to State-of-the-Art Experimental Models

Constant

Rajsfus²,

Carneiro³

et al. 2021

Front. Microbiol.

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Chikungunya virus (CHIKV) is currently one of the most relevant arboviruses to public health. It is a member of the Togaviridae family and alphavirus genus and causes an arthritogenic disease known as chikungunya fever (CHIKF). It is characterized by a multifaceted disease, which is distinguished from other arbovirus infections by the intense and debilitating arthralgia that can last for months or years in some individuals. Despite the great social and economic burden caused by CHIKV infection, there is no vaccine or specific antiviral drugs currently available. Recent outbreaks have shown a change in the severity profile of the disease in which atypical and severe manifestation lead to hundreds of deaths, reinforcing the necessity to understand the replication and pathogenesis processes. CHIKF is a complex disease resultant from the infection of a plethora of cell types. Although there are several in vivo models for studying CHIKV infection, none of them reproduces integrally the disease signature observed in humans, which is a challenge for vaccine and drug development. Therefore, understanding the potentials and limitations of the state-of-the-art experimental models is imperative to advance in the field. In this context, the present review outlines the present knowledge on CHIKV epidemiology, replication, pathogenesis, and immunity and also brings a critical perspective on the current in vitro and in vivo state-of-the-art experimental models of CHIKF.

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Section: Immunopathogenesismentioning

confidence: 99%

Section: Innate Immune Systemmentioning

confidence: 99%

Overview on Chikungunya Virus Infection: From Epidemiology to State-of-the-Art Experimental Models

Constant

Rajsfus²,

Carneiro³

et al. 2021

Front. Microbiol.

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“…Monocytes and macrophages play a significant role in the immunopathology of CHIKVrelated arthritis, and both are important for efferocytosis and the resolution of inflammation [28]. Several cytokines and chemokines induced by inflammation are associated with the severity and/or persistence of CHIKV infection-related symptoms [29]. The cytokine profile in CHIKV infection is similar to that in inflammatory arthritis [1,30,31], which may explain the similarities between the pathogenesis and clinical features of CHIKV-associated arthropathy and those of RA and SpA.…”

Section: Discussionmentioning

confidence: 98%

Rheumatic manifestations of Chikungunya virus infection: Prevalence, patterns, and enthesitis

et al. 2021

Self Cite

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Chikungunya virus (CHIKV) is an arthropod-borne virus transmitted by mosquitoes of the genus Aedes. CHIKV infection causes various rheumatic symptoms, including enthesitis; however, these effects are rarely investigated. The aim of this study was to describe the rheumatic manifestations in CHIKV infection, estimate the prevalence of enthesitis in CHIKV-infected patients, and determine the factors associated with CHIKV-induced enthesitis. We conducted a prospective, observational study in patients with CHIKV infection confirmed by positive RT-PCR or IgM assay from October 2019 to March 2020. Patients with pre-existing inflammatory rheumatic diseases were excluded. A rheumatologist evaluated the demographic and clinical characteristics of the patients, including the number of inflamed joints, enthesitis sites, tendinitis, and tenosynovitis. The Leeds enthesitis index (LEI) and the Maastricht ankylosing spondylitis enthesis score (MASES) were used to evaluate enthesitis sites. Factors associated with enthesitis were determined using logistic regression analysis. One hundred and sixty-four participants diagnosed with CHIKV infection were enrolled. The mean (SD) age of the patients was 48.2 (14) years. The most common pattern of rheumatic manifestations was polyarthritis with or without enthesitis. Enthesitis was observed in 63 patients (38.4%). The most common site of enthesitis was the left lateral epicondyle as assessed by LEI and the posterior superior iliac spine as assessed by MASES. Multivariate analysis indicated that the number of actively inflamed joints and Thai-HAQ score at the initial evaluation were significantly associated with the presence of enthesitis. The main rheumatic manifestations of CHIKV infection were arthritis/arthralgia, with enthesitis as a prominent extraarticular feature. CHIKV infection can cause enthesitis at peripheral and axial sites. We found that enthesitis was associated with a high number of inflamed joints and reduced physical function. These results indicate that the assessment of enthesitis should be considered when monitoring disease activity and as a treatment response parameter in CHIKV-infected patients.

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“…These inflammatory mediators are also demonstrated to be involved in CHIKV induced inflammation with elevated levels of IL-6 and TNF-α in CHIKV-infected macrophage cell lines (28). The levels of the cytokines is often associated with severity of the viral infection (53). Accordingly, treatment with AG and GW increased the levels of TNF-α and IL-6 which was reduced remarkably after the treatment of TM.…”

Section: Tripathi Etal Have Shown Inhibition Of Chikv-nsp2 Protein By Tm With Reduction In Chikvmentioning

confidence: 95%

Telmisartan restricts Chikungunya virus infection in vitro and in vivo through the AT1/ PPAR-γ/MAPKs pathways

Mamidi

Ghosh

et al. 2021

Preprint

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Chikungunya virus (CHIKV) has re-emerged as a global public health threat. The inflammatory pathways of RAS and PPAR-γ are usually involved in viral infections. Thus, Telmisartan (TM) with known capacity to block AT1 receptor and activate PPAR-γ, was investigated against CHIKV. The anti-CHIKV effect of TM was investigated in vitro (Vero, RAW 264.7 cells and hPBMCs) and in vivo (C57BL/6 mice). TM was found to abrogate CHIKV infection efficiently (IC50 of 15.34-20.89µM in the Vero and RAW 264.7 cells respectively). Viral RNA and proteins were reduced remarkably with the TM driven modulation of host m-TOR signaling. Additionally, TM interfered in the early and late stages of CHIKV life cycle with efficacy in both pre and post-treatment assay. Moreover, the agonist of AT1 receptor and antagonist of PPAR-γ increased CHIKV infection suggesting TM’s anti-viral potential by modulating host factors. Besides, reduced activation of all major MAPKs, NF-κB (p65) and cytokines by TM through the inflammatory axis supported the fact that the anti-CHIKV efficacy of TM is partly mediated through the AT1/PPAR-γ/MAPKs pathways. Interestingly, at the human equivalent dose, TM abrogated CHIKV infection and inflammation significantly leading to reduced clinical score and complete survival of C57BL/6 mice. Additionally, TM reduced infection in hPBMC derived monocyte-macrophage populations in vitro. Hence, TM was found to reduce CHIKV infection by targeting both viral and host factors. Considering its safety and in vivo efficacy, it can be a suitable candidate in future for repurposing against CHIKV.

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Cytokines and Chemokines in Chikungunya Virus Infection: Protection or Induction of Pathology

Cited by 31 publications

References 48 publications

Overview on Chikungunya Virus Infection: From Epidemiology to State-of-the-Art Experimental Models

Overview on Chikungunya Virus Infection: From Epidemiology to State-of-the-Art Experimental Models

Rheumatic manifestations of Chikungunya virus infection: Prevalence, patterns, and enthesitis

Telmisartan restricts Chikungunya virus infection in vitro and in vivo through the AT1/ PPAR-γ/MAPKs pathways

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