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 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 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 Antiviral Functions of Monoclonal Antibodies against Chikungunya Virus

Viruses ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 305 ◽  
Author(s):  
Jing Jin ◽  
Graham Simmons
Keyword(s):  
Immune Response ◽  
Monoclonal Antibodies ◽  
Chikungunya Virus ◽  
Therapeutic Antibodies ◽  
Mechanistic Studies ◽  
Chikv Infection ◽  
The Past ◽  
New Generation ◽  
Human And Mouse

Chikungunya virus (CHIKV) is the most common alphavirus infecting humans worldwide. Antibodies play pivotal roles in the immune response to infection. Increasingly, therapeutic antibodies are becoming important for protection from pathogen infection for which neither vaccine nor treatment is available, such as CHIKV infection. The new generation of ultra-potent and/or broadly cross-reactive monoclonal antibodies (mAbs) provides new opportunities for intervention. In the past decade, several potent human and mouse anti-CHIKV mAbs were isolated and demonstrated to be protective in vivo. Mechanistic studies of these mAbs suggest that mAbs exert multiple modes of action cooperatively. Better understanding of these antiviral mechanisms for mAbs will help to optimize mAb therapies.

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

Pathogens ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 415
Author(s):  
Chintana Chirathaworn ◽  
Jira Chansaenroj ◽  
Yong Poovorawan
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Responses ◽  
Chikungunya Virus ◽  
Inflammatory Responses ◽  
Clinical Manifestations ◽  
Joint Inflammation ◽  
Chikv Infection ◽  
Chemokine Production ◽  
Persistent Symptoms ◽  
Cytokines And Chemokines

Chikungunya virus (CHIKV) infection has been commonly detected in tropical countries. The clinical manifestations of CHIKV infection are similar to those of rheumatoid arthritis. Outbreaks of CHIKV infection in Thailand have been reported, and the inductions of various cytokines and chemokines in CHIKV patients during those outbreaks have been shown. Although immune responses in CHIKV infection have been increasingly reported, the mechanisms associated with pathology induction are still not clearly understood. This review focuses on cytokine and chemokine production in CHIKV infection, in association with the severity of joint inflammation. Several cytokines and chemokines involved in the induction or regulation of inflammatory responses were shown to associate with the severe and persistent symptoms in CHIKV infection. Further studies on the difference in immune responses observed in an autoimmune disease, rheumatoid arthritis, infectious disease, and CHIKV infection, would provide additional insights useful for proper CHIKV therapy, especially in patients with severe joint pains.

scholarly journals Chikungunya Outbreak in Kedougou, Southeastern Senegal in 2009–2010

2017 ◽  
Vol 5 (1) ◽  
Author(s):  
Abdourahmane Sow ◽  
Oumar Faye ◽  
Mawlouth Diallo ◽  
Diawo Diallo ◽  
Rubing Chen ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Chikungunya Virus ◽  
Virus Isolation ◽  
Clinical Manifestations ◽  
Serum Samples ◽  
Chikv Infection ◽  
Sylvatic Cycle ◽  
Transmission Cycle ◽  
Significant Difference ◽  
Domestic Cycle

Abstract Background In Senegal, Chikungunya virus (CHIKV), which is an emerging mosquito-borne alphavirus, circulates in a sylvatic and urban/domestic cycle and has caused sporadic human cases and epidemics since 1960s. However, the real impact of the CHIKV sylvatic cycle in humans and mechanisms underlying its emergence still remains unknown. Methodology One thousand four hundred nine suspect cases of CHIKV infection, recruited from 5 health facilities located in Kedougou region, south-eastern Senegal, between May 2009 to March 2010, together with 866 serum samples collected from schoolchildren from 4 elementary schools in May and November 2009 from Kedougou were screened for anti-CHIKV immunoglobulin (Ig)M antibodies and, when appropriate, for viral nucleic acid by real-time polymerase chain reaction (rPCR) and virus isolation. In addition, mosquitoes collected in the same area from May 2009 to January 2010 were tested for CHIKV by rPCR and by virus isolation, and 116 monkeys sera collected from March 2010 to May 2010 were tested for anti-CHIKV IgM and neutralizing antibodies. Results The main clinical manifestations of the CHIKV suspect cases were headache, myalgia, and arthralgia. Evidence for CHIKV infection was observed in 1.4% (20 of 1409) of patients among suspect cases. No significant difference was observed among age or sex groups. In addition, 25 (2.9%) students had evidence of CHIKV infection in November 2009. Chikungunya virus was detected in 42 pools of mosquitoes, mainly from Aedes furcifer, and 83% of monkeys sampled were seropositive. Conclusions Our findings further documented that CHIKV is maintained in a sylvatic transmission cycle among monkeys and Aedes mosquitoes in Kedougou, and humans become infected by exposure to the virus in the forest.

scholarly journals The Phosphatidylserine Receptor TIM-1 Enhances Authentic Chikungunya Virus Cell Entry

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1828
Author(s):  
Jared Kirui ◽  
Yara Abidine ◽  
Annasara Lenman ◽  
Koushikul Islam ◽  
Yong-Dae Gwon ◽  
...  
Keyword(s):  
Chikungunya Virus ◽  
Molecular Mechanisms ◽  
Rna Virus ◽  
Ectopic Expression ◽  
Point Mutations ◽  
Cell Entry ◽  
Target Cells ◽  
Human Hepatoma Cells ◽  
Chikv Infection ◽  
Phosphatidylserine Receptor

Chikungunya virus (CHIKV) is a re-emerging, mosquito-transmitted, enveloped positive stranded RNA virus. Chikungunya fever is characterized by acute and chronic debilitating arthritis. Although multiple host factors have been shown to enhance CHIKV infection, the molecular mechanisms of cell entry and entry factors remain poorly understood. The phosphatidylserine-dependent receptors, T-cell immunoglobulin and mucin domain 1 (TIM-1) and Axl receptor tyrosine kinase (Axl), are transmembrane proteins that can serve as entry factors for enveloped viruses. Previous studies used pseudoviruses to delineate the role of TIM-1 and Axl in CHIKV entry. Conversely, here, we use the authentic CHIKV and cells ectopically expressing TIM-1 or Axl and demonstrate a role for TIM-1 in CHIKV infection. To further characterize TIM-1-dependent CHIKV infection, we generated cells expressing domain mutants of TIM-1. We show that point mutations in the phosphatidylserine binding site of TIM-1 lead to reduced binding, entry, and infection of CHIKV. Ectopic expression of TIM-1 renders immortalized keratinocytes permissive to CHIKV, whereas silencing of endogenously expressed TIM-1 in human hepatoma cells reduces CHIKV infection. Altogether, our findings indicate that, unlike Axl, TIM-1 readily promotes the productive entry of authentic CHIKV into target cells.

scholarly journals BHK-21 Cell Clones Differ in Chikungunya Virus Infection and MXRA8 Receptor Expression

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 949
Author(s):  
Peiqi Yin ◽  
Margaret Kielian
Keyword(s):  
Cell Lines ◽  
Primary Infection ◽  
Sindbis Virus ◽  
Chikungunya Virus ◽  
Mrna Level ◽  
Receptor Expression ◽  
Chikv Infection ◽  
Cell Clones ◽  
Clonal Cell Lines ◽  
Exogenous Expression

Baby hamster kidney-21 (BHK-21) cells are widely used to propagate and study many animal viruses using infection and transfection techniques. Among various BHK-21 cell clones, the fibroblast-like BHK-21/C-13 line and the epithelial-like BHK-21/WI-2 line are commonly used cell clones for alphavirus research. Here we report that BHK-21/WI-2 cells were significantly less susceptible to primary infection by the alphavirus chikungunya virus (CHIKV) than were BHK-21/C-13 cells. The electroporation efficiency of alphavirus RNA into BHK-21/WI-2 was also lower than that of BHK-21/C-13. The growth of CHIKV was decreased in BHK-21/WI-2 compared to BHK-21/C-13, while primary infection and growth of the alphavirus Sindbis virus (SINV) were equivalent in the two cell lines. Our results suggested that CHIKV entry could be compromised in BHK-21/WI-2. Indeed, we found that the mRNA level of the CHIKV receptor MXRA8 in BHK-21/WI-2 cells was much lower than that in BHK-21/C-13 cells, and exogenous expression of either human MXRA8 or hamster MXRA8 rescued CHIKV infection. Our results affirm the importance of the MXRA8 receptor for CHIKV infection, and document differences in its expression in two clonal cell lines derived from the original BHK-21 cell cultures. Our results also indicate that CHIKV propagation and entry studies in BHK-21 cells will be significantly more efficient in BHK-21/C-13 than in BHK-21/WI-2 cells.

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 Chikungunya Manifestations and Viremia in Patients Who Presented to the Fever Clinic at Bangkok Hospital for Tropical Diseases during the 2019 Outbreak in Thailand

2021 ◽  
Vol 6 (1) ◽  
pp. 12
Author(s):  
Hisham A Imad ◽  
Juthamas Phadungsombat ◽  
Emi E Nakayama ◽  
Sajikapon Kludkleeb ◽  
Wasin Matsee ◽  
...  
Keyword(s):  
Chikungunya Virus ◽  
Clinical Manifestations ◽  
Clinical Findings ◽  
Acute Stage ◽  
Tropical Diseases ◽  
Healthy Individuals ◽  
Rt Pcr ◽  
Viral Loads ◽  
The Family ◽  
Systemic Symptoms

Chikungunya virus is an Alphavirus belonging to the family Togaviridae that is transmitted to humans by an infected Aedes mosquito. Patients develop fever, inflammatory arthritis, and rash during the acute stage of infection. Although the illness is self-limiting, atypical and severe cases are not uncommon, and 60% may develop chronic symptoms that persist for months or even for longer durations. Having a distinct periodical epidemiologic outbreak pattern, chikungunya virus reappeared in Thailand in December 2018. Here, we describe a cohort of acute chikungunya patients who had presented to the Bangkok Hospital for Tropical Diseases during October 2019. Infection was detected by a novel antigen kit and subsequently confirmed by real-time RT-PCR using serum collected at presentation to the Fever Clinic. Other possible acute febrile illnesses such as influenza, dengue, and malaria were excluded. We explored the sequence of clinical manifestations at presentation during the acute phase and associated the viral load with the clinical findings. Most of the patients were healthy individuals in their forties. Fever and arthralgia were the predominant clinical manifestations found in this patient cohort, with a small proportion of patients with systemic symptoms. Higher viral loads were associated with arthralgia, and arthralgia with the involvement of the large joints was more common in female patients.

Abstract P469: Scale-up And Characterization Of Therapeutic Mesenchymal Stromal Cell-derived Extracellular Vesicles

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Selen Uman ◽  
Jason A Burdick
Keyword(s):  
Cell Culture ◽  
Extracellular Vesicles ◽  
Animal Studies ◽  
Scale Up ◽  
Spinner Flask ◽  
Perfusion Bioreactor ◽  
Large Animal ◽  
Culture Methods ◽  
Therapeutic Benefits ◽  
Cell Culture Methods

Introduction: Early studies have shown therapeutic benefits of mesenchymal stromal cells (MSCs) in cardioprotection due to their angiogenic, proliferative, anti-apoptotic and anti-inflammatory properties, which are now attributed to secreted factors such as extracellular vesicles (EVs). While MSC-EVs have shown promise in small animals for cardiovascular therapies, large animal studies are required to evaluate the therapeutic benefit of MSC-EVs for clinical translation. One of the biggest challenges for large animal studies is the need to generate clinically-relevant quality and quantity of EVs without batch-to-batch variations that could compromise efficacy. This study aims to explore three different cell culture methods (traditionally-used tissue culture plates (TCP), 3-D printed bioscaffolds in a perfusion system (P), and microcarriers in dynamic spinner flask conditions (M)) to scale-up the production of MSC-EVs across four different biological donors and rigorously investigate EV yield, size, shape, and content. Methods: MSCs were isolated from the iliac crest of four different Yucatan minipigs using heparinized syringes, and cells were expanded to passage four, at which point they were seeded onto the respective cell culture methods. EVs were collected from conditioned medium (CM) via differential ultracentrifugation. EV size, distribution, yield, and protein concentration were studied using Nanoparticle Tracking Analysis (NTA) and microBCA assays. Results: Both perfusion bioreactor and spinner flask systems enabled sustained maintenance of large numbers of cells. Across biological donors and fabrication methods, modes remained within 50-150 nm and were not statistically different. Microcarrier-based spinner flasks and perfusion bioreactor set-ups both improved EV yield, up to 6 times in efficiency. Ongoing research focuses on examining differences in EV content across biological donors using RNA-sequencing and proteomics.

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