scholarly journals A Review of Chikungunya Virus-induced Arthralgia: Clinical Manifestations, Therapeutics, and Pathogenesis

2016 ◽  
Vol 10 (1) ◽  
pp. 129-140 ◽  
Author(s):  
Brad A. Goupil ◽  
Christopher N. Mores
Keyword(s):  
Clinical Research ◽  
Chikungunya Virus ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Western Hemisphere ◽  
Joint Disease ◽  
Chikv Infection ◽  
Initial Infection ◽  
Current State

Background:Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that circulates predominantly in tropical and subtropical regions, potentially affecting over 1 billion people. Recently, an outbreak began in the western hemisphere and has resulted in over 1.8 million reported suspected cases. Infection often results in severe fever, rash and debilitating polyarthralgia lasting weeks to months. Additionally, the current literature reports that CHIKV can result in a severe chronic arthralgia and/or arthritis that can last months to years following the initial infection.Objective:The purpose of this review is to evaluate the literature and summarize the current state of knowledge regarding CHIKV-associated disease, including clinical presentation, diagnosis, risk factors for development of severe disease, treatment, and pathogenesis in human patients. Additionally, recommendations are presented regarding avenues for clinical research to help further elucidate the pathogenesis of joint disease associated with CHIKV infection.Conclusion:While there is an association between initial CHIKV infection and acute disease, a causal relationship with development of chronic arthralgia has not been established at this time. Potential causes of chronic CHIKV-induced arthritis have been postulated, including viral persistence, induction of autoimmune disease, and exacerbation of pre-existing joint disease. While there are numerous reports of chronic CHIKV-associated arthralgia and/or arthritis, there is currently no evidence of a definitive link between initial infection and development of chronic disease. Additional, prospective clinical research on CHIKV-associated disease is necessary to further determine the potential role of virus and development of chronic joint disease.

scholarly journals Insights into Antibody-Mediated Alphavirus Immunity and Vaccine Development Landscape

2021 ◽  
Vol 9 (5) ◽  
pp. 899
Author(s):  
Anthony Torres-Ruesta ◽  
Rhonda Sin-Ling Chee ◽  
Lisa F.P. Ng
Keyword(s):  
Diagnostic Tests ◽  
Inflammatory Arthritis ◽  
Chikungunya Virus ◽  
Vaccine Development ◽  
Antibody Responses ◽  
Chikv Infection ◽  
Wide Range ◽  
Susceptible Populations ◽  
Humoral Responses

Alphaviruses are mosquito-borne pathogens distributed worldwide in tropical and temperate areas causing a wide range of symptoms ranging from inflammatory arthritis-like manifestations to the induction of encephalitis in humans. Historically, large outbreaks in susceptible populations have been recorded followed by the development of protective long-lasting antibody responses suggesting a potential advantageous role for a vaccine. Although the current understanding of alphavirus antibody-mediated immunity has been mainly gathered in natural and experimental settings of chikungunya virus (CHIKV) infection, little is known about the humoral responses triggered by other emerging alphaviruses. This knowledge is needed to improve serology-based diagnostic tests and the development of highly effective cross-protective vaccines. Here, we review the role of antibody-mediated immunity upon arthritogenic and neurotropic alphavirus infections, and the current research efforts for the development of vaccines as a tool to control future alphavirus outbreaks.

scholarly journals Recent Insight into SARS-CoV2 Immunopathology and Rationale for Potential Treatment and Preventive Strategies in COVID-19

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 224 ◽  
Author(s):  
Sara Lega ◽  
Samuele Naviglio ◽  
Stefano Volpi ◽  
Alberto Tommasini
Keyword(s):  
Severe Disease ◽  
Host Immune System ◽  
Great Effort ◽  
Clinical Observations ◽  
Current State ◽  
Key Factor ◽  
Pharmacologic Treatments ◽  
Immunomodulating Drugs ◽  
Insight Into

As the outbreak of the new coronavirus (SARS-CoV-2) infection is spreading globally, great effort is being made to understand the disease pathogenesis and host factors that predispose to disease progression in an attempt to find a window of opportunity for intervention. In addition to the direct cytopathic effect of the virus, the host hyper-inflammatory response has emerged as a key factor in determining disease severity and mortality. Accumulating clinical observations raised hypotheses to explain why some patients develop more severe disease while others only manifest mild or no symptoms. So far, Covid-19 management remains mainly supportive. However, many researches are underway to clarify the role of antiviral and immunomodulating drugs in changing morbidity and mortality in patients who become severely ill. This review summarizes the current state of knowledge on the interaction between SARS-CoV-2 and the host immune system and discusses recent findings on proposed pharmacologic treatments.

scholarly journals Overproduction of IL-6 and Type-I IFN in a Lethal Case of Chikungunya Virus Infection in an Elderly Man During the 2017 Italian Outbreak

2018 ◽  
Vol 5 (11) ◽  
Author(s):  
Francesca Colavita ◽  
Serena Vita ◽  
Eleonora Lalle ◽  
Fabrizio Carletti ◽  
Licia Bordi ◽  
...  
Keyword(s):  
Chikungunya Virus ◽  
Strong Increase ◽  
Type I ◽  
Type I Ifn ◽  
Chikv Infection ◽  
Clinical Presentations ◽  
Abnormal Pattern ◽  
Disease Analysis

Abstract Chikungunya fever is caused by Chikungunya virus (CHIKV) and is generally considered a self-limiting disease. However, severe clinical presentations with a high mortality rate have been reported in association with underlying medical conditions. This study reports the molecular characterization of the virus and an abnormal pattern of circulating cytokines in a unique lethal CHIKV case during the 2017 outbreak in Italy, which involved an elderly patient with underlying cardiac disease. Analysis of inflammatory cytokines revealed a strong increase of interferon (IFN)-α and IFN-β, as well as interleukin-6, suggesting a possible role of type-I IFN in the cytokine storm, which may be correlated with unfavorable prognosis of CHIKV infection.

Analysis of antibody response (IgM, IgG, IgG3) to Chikungunya virus using panel of peptides derived from envelope protein for serodiagnosis

2014 ◽  
Vol 52 (2) ◽  
Author(s):  
Priyanka Verma ◽  
Santwana Bhatnagar ◽  
Pradeep Kumar ◽  
Vinita Chattree ◽  
M.M. Parida ◽  
...  
Keyword(s):  
Antibody Response ◽  
Envelope Protein ◽  
Chikungunya Virus ◽  
Humoral Response ◽  
Protective Role ◽  
Diagnostic Purpose ◽  
Chikv Infection ◽  
Insight Into ◽  
Immunodominant Epitopes

AbstractMany epidemic outbreaks of Chikungunya fever (CHIKF) have been reported throughout the world including India after its reemergence in 2005. The immuno protective role of envelope proteins during Chikungunya virus (CHIKV) infection has been reported. With the aim of identifying the immunodominant epitopes within the envelope protein we investigated the detailed analysis of fine specificity of antibody response in different individuals during CHIKV infection.The peptides corresponding to the full length of E1, E2 and E3 proteins of S27 strain of CHIKV were synthesized and their seroreactivity with CHIKV positive patients’ sera collected from different epidemic regions of India was determined using indirect ELISA.The data analysis reveals many potent epitopes throughout the length of envelope E2 protein thus displaying it as the most promising antigen for diagnostic purpose. We found that the main IgG isotype response to envelope protein was predominantly of subclass IgG3. Interestingly, most of the epitopes were found to be conserved for detecting IgM, IgG and IgG3 antibody response.Peptides E2P3, E2P7, E2P16 and E2P17 were revealed as the most immunodominant peptides that together can form the basis for designing an accurate, economical and easy to synthesize a peptide-based immunodiagnostic for CHIKV. This study provides new and important insight into the humoral response generated by CHIKV S27 strain during the early phase of infection.

scholarly journals Interferon Response Factors 3 and 7 Protect against Chikungunya Virus Hemorrhagic Fever and Shock

2012 ◽  
Vol 86 (18) ◽  
pp. 9888-9898 ◽  
Author(s):  
Penny A. Rudd ◽  
Jane Wilson ◽  
Joy Gardner ◽  
Thibaut Larcher ◽  
Candice Babarit ◽  
...  
Keyword(s):  
Chikungunya Virus ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Interferon Response ◽  
Wild Type ◽  
Chikv Infection ◽  
Response Factors ◽  
Adult Mice

Chikungunya virus (CHIKV) infections can produce severe disease and mortality. Here we show that CHIKV infection of adult mice deficient in interferon response factors 3 and 7 (IRF3/7−/−) is lethal. Mortality was associated with undetectable levels of alpha/beta interferon (IFN-α/β) in serum, ∼50- and ∼10-fold increases in levels of IFN-γ and tumor necrosis factor (TNF), respectively, increased virus replication, edema, vasculitis, hemorrhage, fever followed by hypothermia, oliguria, thrombocytopenia, and raised hematocrits. These features are consistent with hemorrhagic shock and were also evident in infected IFN-α/β receptor-deficient mice.In situhybridization suggested CHIKV infection of endothelium, fibroblasts, skeletal muscle, mononuclear cells, chondrocytes, and keratinocytes in IRF3/7−/−mice; all but the latter two stained positive in wild-type mice. Vaccination protected IRF3/7−/−mice, suggesting that defective antibody responses were not responsible for mortality. IPS-1- and TRIF-dependent pathways were primarily responsible for IFN-α/β induction, with IRF7 being upregulated >100-fold in infected wild-type mice. These studies suggest that inadequate IFN-α/β responses following virus infection can be sufficient to induce hemorrhagic fever and shock, a finding with implications for understanding severe CHIKV disease and dengue hemorrhagic fever/dengue shock syndrome.

scholarly journals Atypical Chikungunya virus infections: clinical manifestations, mortality and risk factors for severe disease during the 2005–2006 outbreak on Réunion

2008 ◽  
Vol 137 (4) ◽  
pp. 534-541 ◽  
Author(s):  
A. ECONOMOPOULOU ◽  
M. DOMINGUEZ ◽  
B. HELYNCK ◽  
D. SISSOKO ◽  
O. WICHMANN ◽  
...  
Keyword(s):  
Risk Factors ◽  
Chikungunya Virus ◽  
Viral Infections ◽  
Case Reports ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Chikungunya Fever ◽  
Course Of Illness ◽  
Atypical Case ◽  
Incidence And Mortality

SUMMARYIn April 2005, an outbreak of Chikungunya fever occurred on the island of Réunion in the Indian Ocean. During winter 2005, six patients developed meningoencephalitis and acute hepatitis due to Chikungunya virus. Our objectives were to determine the incidence and mortality of atypical Chikungunya viral infections and to identify risk factors for severe disease. A hospital-based surveillance system was established to collect data on atypical Chikungunya cases. Case reports, medical records and laboratory results were reviewed and analysed. We defined an atypical case as one in which a patient with laboratory-confirmed Chikungunya virus infection developed symptoms other than fever and arthralgia. We defined a severe atypical case as one which required maintenance of at least one vital function. We recorded 610 atypical cases of Chikungunya fever: 222 were severe cases, 65 affected patients died. Five hundred and forty-six cases had underlying medical conditions (of which 226 suffered from cardiovascular, 147 from neurological and 150 from respiratory disorders). Clinical features that had never been associated with Chikungunya fever were recorded, such as bullous dermatosis, pneumonia, and diabetes mellitus. Hypertension, and underlying respiratory or cardiological conditions were independent risk factors for disease severity. The overall mortality rate was 10·6% and it increased with age. This is the first time that severe cases and deaths due to Chikungunya fever have been documented. The information presented in this article may assist clinicians in identifying the disease, selecting the treatment strategy, and anticipating the course of illness.

scholarly journals Treatment of Chikungunya Virus (CHIKV) Using Targeted Immunotherapy

2021 ◽  
Author(s):  
Fleury Augustin Nsole Biteghe ◽  
Chalomie Nyangone Ekome Toung ◽  
Jean De La Croix Ndong ◽  
Neelakshi Mungra ◽  
Tahir B. Dar ◽  
...  
Keyword(s):  
Animal Studies ◽  
Chikungunya Virus ◽  
Clinical Manifestations ◽  
Chikv Infection ◽  
Prophylactic Efficacy ◽  
Multiple Factors ◽  
Therapeutic Benefits ◽  
Infection Dynamics ◽  
Human And Mouse ◽  
Targeted Immunotherapy

Chikungunya virus (CHIKV) is the most common mosquito-borne Alphavirus infecting humans worldwide. Up to date, there are no antiviral treatments or vaccines approved to treat or prevent CHIKV for which treatments remain symptomatic based on clinical manifestations. Hence, designing effective therapies to either prevent or treat CHIKV infection is of paramount importance. Interestingly, monoclonal antibodies (mAbs) are known to be significantly important in mediating protective immunity in CHIV infection. During the last decades, numerous animal studies have reported the protective and prophylactic efficacy of human and mouse anti-CHIKV mAbs isolated from convalescent patients. However, the therapeutic benefits of these anti-CHIKV mAbs can be limited by multiple factors. Thus, it becomes pertinent to better understand the CHIKV infection dynamics, mitigate the undesired mAbs-associated effects and improve therapies. In this review, we critically discuss CHIKV antiviral infectious mechanisms and address how the improved understanding of the latter may pave the way to better targeted immunotherapies.

scholarly journals New Insights into Chikungunya Virus Infection and Pathogenesis

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Vasiliya Kril ◽  
Olivier Aïqui-Reboul-Paviet ◽  
Laurence Briant ◽  
Ali Amara
Keyword(s):  
Chikungunya Virus ◽  
Molecular Mechanisms ◽  
Clinical Manifestations ◽  
Annual Review ◽  
Publication Date ◽  
Nonstructural Proteins ◽  
Chikv Infection ◽  
Replication Complex ◽  
Host Cell Interactions ◽  
Patients Experience

Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus responsible for major outbreaks of disease since 2004 in the Indian Ocean islands, South east Asia, and the Americas. CHIKV causes debilitating musculoskeletal disorders in humans that are characterized by fever, rash, polyarthralgia, and myalgia. The disease is often self-limiting and nonlethal; however, some patients experience atypical or severe clinical manifestations, as well as a chronic rheumatic syndrome. Unfortunately, no efficient antivirals against CHIKV infection are available so far, highlighting the importance of deepening our knowledge of CHIKV host cell interactions and viral replication strategies. In this review, we discuss recent breakthroughs in the molecular mechanisms that regulate CHIKV infection and lay down the foundations to understand viral pathogenesis. We describe the role of the recently identified host factors co-opted by the virus for infection and pathogenesis, and emphasize the importance of CHIKV nonstructural proteins in both replication complex assembly and host immune response evasion. Expected final online publication date for the Annual Review of Virology, Volume 8 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals The native European Aedes geniculatus mosquito species can transmit Chikungunya virus

2019 ◽  
Author(s):  
Jorian Prudhomme ◽  
Albin Fontaine ◽  
Guillaume Lacour ◽  
Jean-Charles Gantier ◽  
Laure Diancourt ◽  
...  
Keyword(s):  
Chikungunya Virus ◽  
Vector Competence ◽  
Mosquito Species ◽  
Cumulative Distribution ◽  
Mosquito Vector ◽  
Indigenous Species ◽  
Chikv Infection ◽  
Invasive Mosquito ◽  
Virus Emergence

AbstractEurope is the world’s leading tourism destination and is receiving every year travelers from areas with active arbovirus transmission. There is thus a threat of mosquito-borne virus emergence in Europe due to the presence of the invasive mosquito vector Aedes albopictus. Little attention has been paid about the possible role of indigenous mosquito species as vectors of emerging arboviruses. Here, we assessed the vector competence dynamic of Ae. geniculatus, a European anthropophilic mosquito species, for chikungunya virus (CHIKV) in comparison with Ae. albopictus.We revealed that Ae. geniculatus was highly susceptible to CHIKV infection and could transmit the virus. By specifically exploring the vector competence dynamic in both mosquito species, we revealed that the cumulative distribution of CHIKV incubation period in Ae. geniculatus was delayed by several days as compared to Ae. albopictus.Our results strengthen the importance of considering indigenous species as potential vectors for emerging arboviruses. They also revealed the importance of considering variation in arbovirus dissemination or transmission dynamics in mosquitoes when performing vector competence assays. We will discuss the implications of our results on a CHIKV outbreak dynamic in a theoretical framework.Sentence summaryThe European mosquito Aedes geniculatus is highly susceptible to CHIKV infection but disseminate and transmit the virus several days later than Ae. albopictus.

scholarly journals Expanding Regulatory T Cells Alleviates Chikungunya Virus-Induced Pathology in Mice

2015 ◽  
Vol 89 (15) ◽  
pp. 7893-7904 ◽  
Author(s):  
Wendy W. L. Lee ◽  
Teck-Hui Teo ◽  
Zhisheng Her ◽  
Fok-Moon Lum ◽  
Yiu-Wing Kam ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Chikungunya Virus ◽  
Interleukin 2 ◽  
Joint Inflammation ◽  
Chikv Infection ◽  
Joint Pathology ◽  
Alternative Approach ◽  
Control Virus

ABSTRACTChikungunya virus (CHIKV) infection is a reemerging pandemic human arboviral disease. CD4+T cells were previously shown to contribute to joint inflammation in the course of CHIKV infection in mice. The JES6-1 anti-IL-2 antibody selectively expands mouse regulatory T cells (Tregs) by forming a complex with IL-2. In this study, we show that the IL-2 JES6-1-mediated expansion of Tregs ameliorates CHIKV-induced joint pathology. It does so by inhibiting the infiltration of CD4+T cells due to the induction of anergy in CHIKV-specific CD4+effector T cells. These findings suggest that activation of Tregs could also become an alternative approach to control CHIKV-mediated disease.IMPORTANCEChikungunya virus (CHIKV) has reemerged as a pathogen of global significance. Patients infected with CHIKV suffer from incapacitating joint pain that severely affects their daily functioning. Despite the best efforts, treatment is still inadequate. While T cell-mediated immunopathology in CHIKV infections has been reported, the role of regulatory T cells (Tregs) has not been explored. The JES6-1 anti-interleukin 2 (IL-2) antibody has been demonstrated to selectively expand mouse Tregs by forming a complex with IL-2. We reveal here that IL-2 JES6-1-mediated expansion of Tregs ameliorates CHIKV-induced joint pathology in mice by neutralizing virus-specific CD4+effector T (Teff) cells. We show that this treatment abrogates the infiltration of pathogenic CD4+T cells through induction of anergy in CHIKV-specific CD4+Teff cells. This is the first evidence where the role of Tregs is demonstrated in CHIKV pathogenesis, and its expansion could control virus-mediated immunopathology.

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