Chikungunya virus (CHIKV) is an alphavirus transmitted mainly by female mosquitoes of the species Aedes aegypti and Aedes albopictus.It causes an acute disease characterized by fever, arthralgia and in some cases a maculopapular rash (Thiberville et al., 2013).Infection is rarely fatal, but in many cases it evolves into a chronic stage of persistent disabling polyarthritis . Ravichandran R, Manian M. Ribavirin therapy for Chikungunya arthritis. Found insideThis book provides trajectories and illustrations of viruses that have catapulted into the global arena (linked to humans, animals, and vectors) due to human behaviors in recent years, as well as viruses that have already shown expansion ... Females with an adequate food supply can live up to 5 months or longer, with the average female life span being about 6 weeks. Genome-scale phylogenetic analyses of chikungunya virus reveal independent emergences of recent epidemics and various evolutionary rates. Tsetsarkin KA, Chen R, Weaver SC. Although serological evidence suggests that some antibody-mediated heterologous immunity may be afforded by alphavirus infection, the extent to which broadly neutralizing antibodies that protect against multiple arthritogenic alphaviruses are elicited during natural infection remains unknown. On the right side is the life cycle of chikungunya virus : What we can do ? The disease shares some clinical signs with dengue, and can be . As E1 and E3-E2 transit the secretory pathway (Figure 2), they remain associated as a noncovalent, hetero-oligomeric complex that undergoes conformational changes and posttranslational modifications, including palmitoylation and N-linked glycosylation as well as release of E3 by furin, to form mature spikes at the PM (Figure 2 and refs. Kinne RW, et al. Chikungunya has become widespread many of times beyond our control. Authophagy is proposed to play a global pro-CHIKV function in human cells, possibly by limiting apoptosis, and may be a pathogenesis determinant (95–97). In late 2013, the first local transmission of chikungunya virus in the Americas was identified in Caribbean countries and territories. Acute CHIKV infection elicits robust innate immune responses, leading to elevation of type I IFNs and numerous proinflammatory chemokines, cytokines, and growth factors (Table 2 and refs. Weaver SC. Various CHIKV vaccine strategies have been investigated, with many in preclinical and clinical studies (reviewed in ref. . 166). CHIKV is transmitted by Aedes species of mosquitoes and is capable of an epidemic, urban transmission cycle with high rates of infection. Levitt NH, Ramsburg HH, Hasty SE, Repik PM, Cole FE, Lupton HW. Solignat M, Gay B, Higgs S, Briant L, Devaux C. Replication cycle of chikungunya: a re-emerging arbovirus. Thus, an imbalance of immune mediators required for effective antiviral defense also likely contributes to CHIKV pathogenesis. Gaedigk-Nitschko K, Schlesinger MJ. Chikungunya virus is spread to people by the bite of an infected mosquito. Acute CHIKV infection begins with transmission of the virus via a bite of an infected mosquito to the skin, where it replicates in susceptible cells, including fibroblasts and macrophages. Residue 82 of the Chikungunya virus E2 attachment protein modulates viral dissemination and arthritis in mice. The virus is transmitted during probing and blood feeding. Introduction. Javelle E, Ribera A, Degasne I, Gaüzère BA, Marimoutou C, Simon F. Specific management of post-chikungunya rheumatic disorders: a retrospective study of 159 cases in Reunion Island from 2006–2012. Furthermore, in postexposure therapeutic trials, monoclonal antibodies protect against CHIKV disease in mice, even when administered at late times of infection (160, 161), suggesting that immunotherapy would be effective for treatment of CHIKV infection. IL-1β, IL-6, and RANTES as biomarkers of Chikungunya severity. Stress granule components G3BP1 and G3BP2 play a proviral role early in Chikungunya virus replication. Know more about the symptoms and treatment of Chikungunya in this presentation (PPT). 110). An ECSA strain emerged again during an outbreak in Kenya in late 2004, initiating one of the largest CHIKV epidemics on record, with expansion to areas well beyond the historical range of the virus (4, 32). aegypti and Ae. These structures contain helical tubular arrays of viral glycoproteins within the vesicles, which are studded with nucleocapsids on their cytoplasmic face (91–93). Coincident with rising viral loads and IFN-α responses, the vast majority of infected patients experience sudden onset of clinical illness (Table 1), with a small proportion of infected individuals (5%–28%) remaining asymptomatic (118, 119). 70, 77, 78). Reappearance of chikungunya, formerly called dengue, in the Americas. Early differentiation of chronic CHIKV infection would inform disease management, which may vary according to type. Gibney KB, et al. In recent decades mosquito vectors of chikungunya have spread to Europe and the Americas. 1. Unlike other alphaviruses such as the chikungunya virus, SAV is transmitted without an arthropod vector, and does not cause cell shut-off during infection. Aedes furcifer and other mosquitoes as vectors of chikungunya virus at Mica, northeastern Transvaal, South Africa. Sourisseau M, et al. This model is based on human and animal studies. Following release into the cytoplasm, the nucleocapsid disassembles to deliver genomic viral RNA (vRNA) into the cytosol for translation (77). It is an RNA virus that belongs to the alphavirus genus of the family Togaviridae.The name "chikungunya" derives from a word in the Kimakonde language, meaning "to become contorted", and describes the stooped appearance of sufferers with joint pain (arthralgia). Akahata W, et al. Hawman DW, et al. CHIKV structure, genome, and replication cycle. Atypical symptoms are most prevalent among vulnerable groups, including neonates, the elderly, and those with underlying comorbidities. The vector of Chikungunya virus (CHIKV) in the Americas is the mosquito Aedes aegypti. Dissemination and transmission of the E1-226V variant of chikungunya virus in Aedes albopictus are controlled at the midgut barrier level. Two types of persistent CHIKV-induced rheumatic disorders have been described (131). Mavale M, et al. Treatment is focused on relieving the symptoms. Snyder JE, et al. Chikungunya virus infection results in higher and persistent viral replication in aged rhesus macaques due to defects in anti-viral immunity. Glycoprotein organization of Chikungunya virus particles revealed by X-ray crystallography. Arboviruses can affect both animals (including humans) and plants Akahata W, Nabel GJ. Gérardin P, et al. Dermody, T. Print issue publication. Grandadam M, et al. Model of acute and chronic CHIKV pathogenesis. Inhibition of chikungunya virus replication by harringtonine, a novel antiviral that suppresses viral protein expression. Outbreak of chikungunya virus infection, Vanimo, Papua New Guinea. Venereal transmission of chikungunya virus by Aedes aegypti mosquitoes (Diptera: Culicidae). The female Aedes aegypti lays her eggs separately unlike most species. Mombouli JV, et al. Chikungunya PowerPoint Presentation (PPTs) Chikungunya is spread by mosquitoes and is characterised by severe joint pains with fever. Found inside – Page iiThe viruses are now known to contain a single positive strand of RNA. About 50% of corona virus infections result in clinical illness. About 5% of common colds are caused by strain DC 43 in winter. albopictus. Judith D, et al. Vertical transmission from mother to fetus is rare; transplacental chikungunya transmission and severe congenital chikungunya has been described. The females can produce up to five batches of eggs during a lifetime. A fatal case of chikungunya virus infection with liver involvement. Ashbrook AW, et al. Hepatitis B, hepatitis C and HIV infections are well-known infectious diseases caused by blood products, but recently there have been almost no reports. Plasmacytoid dendritic cells, NK cells, and neutrophils also infiltrate infected tissues during acute CHIKV infection (8, 143–146), but their role in CHIKV control remains to be clarified. Chikungunya virus envelope-specific human monoclonal antibodies with broad neutralization potency. Joubert PE, et al. Species-specific impact of the autophagy machinery on Chikungunya virus infection. Poo YS, et al. The incoming CHIKV genome is directly translated to produce the nonstructural precursor polyprotein P1234, which is cleaved by the virus-encoded protease located in nsP2 into P123 and nsP4 (64, 79). Chua HH, et al. Kam YW, et al. human monoclonal antibodies inhibit chikungunya virus (CHIKV) infection. Chikungunya virus (CHIKV), a reemerging arbovirus, causes a crippling musculoskeletal inflammatory disease in humans characterized by fever, polyarthralgia, myalgia, rash, and headache. Chikungunya Virus Life Cycle in Host Cells. We apologize to all whose work could not be referenced because of formatting and length restrictions. Home. Neutralizing monoclonal antibodies block Chikungunya virus entry and release by targeting an epitope critical to viral pathogenesis. Versatile trans-replication systems for chikungunya virus allow functional analysis and tagging of every replicase protein. Virus titers decline with the development of CHIKV-specific adaptive immunity. Introduction. The emergence of more virulent SARS virus has made scientists look back at other so-called neglected diseases such as dengue, Zika, and chikungunya, etc. During this devastating epidemic, the virus spread to a number of islands in the Indian Ocean, India, and parts of Southeast Asia, leading to over 6 million estimated cases of CHIKV disease (Figure 1 and refs. Not all eggs are laid at once, but they can be spread out over hours or days, depending on the availability of suitable substrates. Found insideThis book presents our understanding of the virus, bringing comprehensive knowledge in a single source. Khan AH, Morita K, Parquet mDel C, Hasebe F, Mathenge EG, Igarashi A. One uses a recombinant baculovirus-insect cell expression system that yields VLPs eliciting strong neutralizing antibodies, which are protective in mice (194). In multiple cohorts, elevated levels of IL-1β, IL-6, and monocyte chemoattractant protein-1 (MCP-1) correlate with disease severity (117, 141), and high levels of IL-6 and GM-CSF correlate with persistent arthralgia (refs. Isolation and characterization of broad and ultrapotent human monoclonal antibodies with therapeutic activity against Chikungunya virus. Teo TH, Lum FM, Lee WW, Ng LF. Overlayed with CHIKV distribution is the geographic range of the two primary vectors responsible for urban mosquito-human-mosquito transmission of the virus. Chikungunya virus: A virus that causes a disease resembling dengue fever, seen mainly in Africa, the Indian subcontinent, the Caribbean, and Southeast Asia.The Chikungunya virus is an arbovirus transmitted by Aedes mosquitoes. In addition, persistent IgM levels have been detected in patients and animals experiencing chronic arthritis (8, 105, 126, 153, 164, 165). Hawman DW, et al. (v) Four nsPs, together with genomic RNA and presumably host proteins, assemble at the plasma membrane (PM) and modify it to form viral replication compartments (spherules) containing viral dsRNA. Utt A, Quirin T, Saul S, Hellström K, Ahola T, Merits A. (March 1, 2017): Genome microevolution of chikungunya viruses causing the Indian Ocean outbreak. Sylvatic transmission of arboviruses among Bornean orangutans. CHIKV replication cycle in mammalian cells. Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells. PgSIT uses a simple CRISPR-based approach to generate... Arthritogenic alphaviruses are globally distributed, mosquito-transmitted viruses that cause rheumatological disease in humans and include Chikungunya virus (CHIKV), Mayaro virus (MAYV), and others. Because of the stooped posture and rigid gait of infected individuals, the disease was given the name chikungunya, a word from the Kimakonde language that translates as “that which bends up” (2). The number of eggs is dependent on the size of the bloodmeal. •Chikungunya has been identified in over 60 countries in Asia, Africa, Europe and the Americas. Chikungunya virus and the mosquito vector Aedes aegypti in New Caledonia (South Pacific Region). Cryo-electron microscopy structures of Fab frag-ments of two human NAbs and chikungunya virus-like particles showed a binding footprint that The eggs of Aedes aegypti are smooth, long, ovoid shaped, and roughly one millimeter long. Chaaitanya IK, et al. Chopra A, Anuradha V, Lagoo-Joshi V, Kunjir V, Salvi S, Saluja M. Chikungunya virus aches and pains: an emerging challenge. This work was supported by Public Health Service awards F32 AI096833 (to LAS), R01 AI123348 (to LAS and TSD), and U54 AI057157 for the Southeast Regional Center of Excellence for Emerging Infections and Biodefense (to LAS and TSD). (iv) Disassembly of the nucleocapsid liberates positive-sense genomic RNA and nonstructural protein (nsP) translation occurs. Antagonism of the Sodium-Potassium ATPase Impairs Chikungunya Virus Infection. Abdelnabi R, Neyts J, Delang L. Towards antivirals against chikungunya virus. HelpDesk: 2-5200. Here, we summarize various vaccine candidates, focusing on those that have advanced to human studies (Table 4). General description and epidemiology. Chikungunya virus is a single-stranded RNA virus that belongs to the family Togaviridae, genus Alphavirus. It has two main types of life cycles, the enzootic/sylvatic cycle (between animals) and the urban/endemic/epidemic cycle . As the common name suggests, Aedes aegypti is the primary vector of yellow fever, a disease . Ozden S, et al. In 2011, hepatitis E virus (HEV) antibody test was covered by insurance in Japan, and certain numbers of transfusion-transmitted HEV were reported, and five cases were recognized in 2019. As an emerging virus, CHIKV imposes a threat to public health. Chen KC, Kam YW, Lin RT, Ng MM, Ng LF, Chu JJ. and a lot more places where rain-water collects or is stored. Free access | 10.1172/JCI84417. Chikungunya fever generally presents with the characteristic fever, headache, nausea and vomiting, body and joint pain, and general malaise. Broeckel R, Haese N, Messaoudi I, Streblow DN. In contrast, strains from the ECSA lineage have repeatedly spread to new regions to cause significant urban epidemics. Metz SW, et al. A number of therapeutic strategies to combat CHIKV have been investigated (reviewed in ref. Although 6K and TF are found at low levels in virion particles (68, 85, 86) and appear to contribute to viral budding (68, 87) and pathogenesis (88), their precise roles in glycoprotein processing, assembly, budding, and particle stability remain to be clarified (67, 68, 88). 101–103). 166). The most common symptoms are fever and joint pain, followed by headache, muscle pain, joint swelling, or rash. In preclinical studies using Ifnar–/– mice, MV-CHIKV elicited robust and cross-neutralizing immune responses that protect against lethal challenge (195). Chikungunya virus is an alpha virus that belongs to the Togaviridae family. Sjöberg M, Garoff H. Interactions between the transmembrane segments of the alphavirus E1 and E2 proteins play a role in virus budding and fusion. The chikungunya virus, transmitted to humans when bitten by mosquitoes of the genus Aedes, causes severe joint pain in patients. 2 Chikungunya virus (CHIKV) is a mosquito-borne alphavirus. Many mouse and human IgM and IgG antibodies broadly and potently neutralize CHIKV (157–162). Post-epidemic Chikungunya disease on Reunion Island: course of rheumatic manifestations and associated factors over a 15-month period. Some strains encode an opal stop codon following nsP3, and low-frequency read-through yields both P123 and P1234 (79). Click here for more information about advertising. Ramsauer K, et al. Chikungunya virus, an enveloped, single-stranded RNA virus. Gérardin P, et al. Type I IFN signaling controls viral replication and pathogenesis during acute infection (104, 114–116). Zika virus: following the path of dengue and chikungunya? The name literally means "that which bends up" and refers to the severe joint pain that often accompanies the illness. Chikungunya virus-induced autophagy delays caspase-dependent cell death. Chikungunya virus is a re-emerging alphavirus that recently caused an epidemic in countries of the Indian Ocean. | Random codon re-encoding induces stable reduction of replicative fitness of Chikungunya virus in primate and mosquito cells. Embedded within the viral envelope are heterodimers of the E1 and E2 glycoproteins arranged in trimers forming an icosahedral lattice (69). Infected travelers often served as sentinels, seeding autochthonous transmission of the virus in naive areas, including in Italy in 2007 (37) and France in 2010 (38). 195). Common elevated immune mediators associated with CHIKV disease in humans. • Established a research portfolio to investigate Chikungunya virus (CHIKV), a mosquito-borne virus. (vi) Spherule internalization allows formation of large cytopathic vacuoles (CPV-1) that house multiple spherules. To complement existing measures, here we develop a molecular genetic control system termed precision-guided sterile insect technique (pgSIT) in Aedes aegypti. Range of Ae. The vast majority of infected individuals develop chikungunya fever, an acute illness notable for rapid onset of fever, incapacitating polyarthralgia and arthritis, rash, myalgia, and headache (Table 1 and ref. DENV causes an estimated 390 million infections per year, of which about 100 million are symptomatic [1]. Ooi YS, Stiles KM, Liu CY, Taylor GM, Kielian M. Genome-wide RNAi screen identifies novel host proteins required for alphavirus entry. Historically, CHIKV has been endemic in tropical and subtropical regions of sub-Saharan Africa and Southeast Asia, where two distinct CHIKV transmission cycles exist. Monocytes and macrophages have been detected in synovial fluid from chronic CHIKV patients (8) and animals (105), and CHIKV RNA and protein are detectable in synovial macrophages from humans (8) and nonhuman primates (NHPs) (105) during the chronic phase of infection. Morrison TE, et al. Nhan TX, Musso D. The burden of chikungunya in the Pacific. 64). •Transmission mostly by Aedes aegypti and Aedes albopictus •Other mosquitoes in Africa can act as efficient vectors for chikungunya: Aedes dalzieli, Aedes furcifer, Aedes taylori, Aedes africanus, and Aedes luteocephalus. CHIKV consists of three related genotypes: Asian, East/Central . This book reviews the current status of antiviral therapy, from the roads to development of new compounds to their clinical use and cost effectiveness. Information Technology Services. Found insideThe perspective represented by this book, that of medical virology as an infectious disease science, is meant to provide a starting point, an anchor, for those who must relate the subject to clinical practice, public health practice, ... Model of acute and chronic CHIKV pathogenesis. Currently, there are no vaccines or antivirals available for the prevention of CHIKV infection. Ross RW. 49). 64). Dupont-Rouzeyrol M, et al. Nougairede A, De Fabritus L, Aubry F, Gould EA, Holmes EC, de Lamballerie X. Functional characterization of the alphavirus TF protein. Attenuation of 181/25 is attributable to only two point mutations in E2 (T12I and G82R) (180); the mutation at residue 82, which enhances glycosaminoglycan binding (74, 75), is the dominant attenuating factor (180). Unconventional repertoire profile is imprinted during acute Chikungunya infection for natural killer cells polarization toward cytotoxicity. Centers for Disease Control and Prevention. Arias-Goeta C, Mousson L, Rougeon F, Failloux AB. This vaccine is the third CHIKV vaccine to enter phase II clinical trials (NCT02861586). Carey DE. Borgherini G, et al. The duplicity and varied manifestations of CHIKV immunopathology pose challenges to the development of effective treatments. After entering the cell, the endosome acidic environment triggers conformational changes with the viral envelope proteins (E1 and E2 complex) reorganizing, leading to dissociation of the E2-E1 heterodimers, and formation of E1 homotrimers. III. Ng LF, et al. Found inside – Page iiThe essential reference of clinical virology Virology is one of the most dynamic and rapidly changing fields of clinical medicine. Thiberville SD, et al. Rajapakse S, Rodrigo C, Rajapakse A. Atypical manifestations of chikungunya infection. Chikungunya virus (CHIKV) is a re-emerging virus that has caused various disease outbreaks in Africa and Asia. Chimeric alphavirus vaccine candidates for chikungunya. 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M, Gay B, Higgs S, Hellström K, Ahola T, S! Of CHIKV infection would inform disease management, which are protective in mice 194!

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