Displaying publications 1 - 20 of 90 in total

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  1. Kang H, Auzenbergs M, Clapham H, Maure C, Kim JH, Salje H, et al.
    Lancet Infect Dis, 2024 May;24(5):488-503.
    PMID: 38342105 DOI: 10.1016/S1473-3099(23)00810-1
    BACKGROUND: Chikungunya is an arboviral disease transmitted by Aedes aegypti and Aedes albopictus mosquitoes with a growing global burden linked to climate change and globalisation. We aimed to estimate chikungunya seroprevalence, force of infection (FOI), and prevalence of related chronic disability and hospital admissions in endemic and epidemic settings.

    METHODS: In this systematic review, meta-analysis, and modelling study, we searched PubMed, Ovid, and Web of Science for articles published from database inception until Sept 26, 2022, for prospective and retrospective cross-sectional studies that addressed serological chikungunya virus infection in any geographical region, age group, and population subgroup and for longitudinal prospective and retrospective cohort studies with data on chronic chikungunya or hospital admissions in people with chikungunya. We did a systematic review of studies on chikungunya seroprevalence and fitted catalytic models to each survey to estimate location-specific FOI (ie, the rate at which susceptible individuals acquire chikungunya infection). We performed a meta-analysis to estimate the proportion of symptomatic patients with laboratory-confirmed chikungunya who had chronic chikungunya or were admitted to hospital following infection. We used a random-effects model to assess the relationship between chronic sequelae and follow-up length using linear regression. The systematic review protocol is registered online on PROSPERO, CRD42022363102.

    FINDINGS: We identified 60 studies with data on seroprevalence and chronic chikungunya symptoms done across 76 locations in 38 countries, and classified 17 (22%) of 76 locations as endemic settings and 59 (78%) as epidemic settings. The global long-term median annual FOI was 0·007 (95% uncertainty interval [UI] 0·003-0·010) and varied from 0·0001 (0·00004-0·0002) to 0·113 (0·07-0·20). The highest estimated median seroprevalence at age 10 years was in south Asia (8·0% [95% UI 6·5-9·6]), followed by Latin America and the Caribbean (7·8% [4·9-14·6]), whereas median seroprevalence was lowest in the Middle East (1·0% [0·5-1·9]). We estimated that 51% (95% CI 45-58) of people with laboratory-confirmed symptomatic chikungunya had chronic disability after infection and 4% (3-5) were admitted to hospital following infection.

    INTERPRETATION: We inferred subnational heterogeneity in long-term average annual FOI and transmission dynamics and identified both endemic and epidemic settings across different countries. Brazil, Ethiopia, Malaysia, and India included both endemic and epidemic settings. Long-term average annual FOI was higher in epidemic settings than endemic settings. However, long-term cumulative incidence of chikungunya can be similar between large outbreaks in epidemic settings with a high FOI and endemic settings with a relatively low FOI.

    FUNDING: International Vaccine Institute.

    Matched MeSH terms: Chikungunya virus/immunology
  2. Tongco AMP, Rivera WL
    Trop Biomed, 2023 Jun 01;40(2):129-137.
    PMID: 37650398 DOI: 10.47665/tb.40.2.002
    Chikungunya virus (CHIKV) is a neglected tropical pathogen that causes fever and long-lasting severe arthralgia. Despite its high morbidity, there is still no licensed specific therapeutic option for it. This study proposes a multi-epitope subunit vaccine candidate for CHIKV, designed using computational methods. It was based on the E2 spike glycoprotein in CHIKV, from which T- and B-cell epitopes were predicted and then refined. The pan HLA DR-binding epitope (PADRE) was added to this refined construct, then simulated compared with the native protein, where it was predicted to elicit more than twice the number of antibody titers. Thus, this construct is potentially effective against CHIKV, which further experimentation using live models would be able to verify. This study also demonstrates the feasibility of using rational tools in the future to further optimize vaccine design.
    Matched MeSH terms: Chikungunya virus*
  3. Khor CS, Teoh BT, Sam SS, Khoo HY, Azizan NS, CheMatSeri A, et al.
    J Infect Dev Ctries, 2023 Jan 31;17(1):118-124.
    PMID: 36795935 DOI: 10.3855/jidc.16613
    INTRODUCTION: Chikungunya fever is a mosquito-borne viral disease that usually presents with prominent arthralgia. An outbreak of chikungunya fever was reported in Tanjung Sepat, Malaysia in 2019. The outbreak was limited in size with a low number of cases being reported. The present study sought to determine the possible variables that could have affected the transmission of the infection.

    METHODOLOGY: A cross-sectional study involving 149 healthy adult volunteers from Tanjung Sepat was performed soon after the outbreak had subsided. All the participants donated blood samples and completed the questionnaires. Laboratory detection of anti-CHIKV IgM and IgG antibodies was performed using enzyme-linked immunoassays (ELISA). Risk factors associated with chikungunya seropositivity were determined using logistic regression.

    RESULTS: The majority (72.5%, n = 108) of the study participants tested positive for CHIKV antibodies. Only 8.3% (n = 9) of the participants out of all the seropositive volunteers had an asymptomatic infection. Participants who resided with a febrile (p < 0.05, Exp(B) = 2.2, confidence interval [CI] 1.3-3.6) or a CHIKV-diagnosed person (p < 0.05, Exp(B) = 2.1, CI 1.2-3.6) in the same household were found likely to be tested positive for CHIKV antibodies.

    CONCLUSIONS: Findings from the study support that asymptomatic CHIKV infections and indoor transmission occurred during the outbreak. Hence, widespread community testing and indoor use of mosquito repellent are among the possible measures that can be implemented to reduce CHIKV transmission during an outbreak.

    Matched MeSH terms: Chikungunya virus*
  4. Dass S, Ngui R, Gill BS, Chan YF, Wan Sulaiman WY, Lim YAL, et al.
    Trans R Soc Trop Med Hyg, 2021 08 02;115(8):922-931.
    PMID: 33783526 DOI: 10.1093/trstmh/trab053
    BACKGROUND: We studied the spatiotemporal spread of a chikungunya virus (CHIKV) outbreak in Sarawak state, Malaysia, during 2009-2010.

    METHODS: The residential addresses of 3054 notified CHIKV cases in 2009-2010 were georeferenced onto a base map of Sarawak with spatial data of rivers and roads using R software. The spatiotemporal spread was determined and clusters were detected using the space-time scan statistic with SaTScan.

    RESULTS: Overall CHIKV incidence was 127 per 100 000 population (range, 0-1125 within districts). The average speed of spread was 70.1 km/wk, with a peak of 228 cases/wk and the basic reproduction number (R0) was 3.1. The highest age-specific incidence rate was 228 per 100 000 in adults aged 50-54 y. Significantly more cases (79.4%) lived in rural areas compared with the general population (46.2%, p<0.0001). Five CHIKV clusters were detected. Likely spread was mostly by road, but a fifth of rural cases were spread by river travel.

    CONCLUSIONS: CHIKV initially spread quickly in rural areas mainly via roads, with lesser involvement of urban areas. Delayed spread occurred via river networks to more isolated areas in the rural interior. Understanding the patterns and timings of arboviral outbreak spread may allow targeted vector control measures at key transport hubs or in large transport vehicles.

    Matched MeSH terms: Chikungunya virus*
  5. Nor Rashid N, Teoh TC, Al-Harbi SJ, Yusof R, Rothan HA
    Trop Biomed, 2021 Mar 01;38(1):36-41.
    PMID: 33797522 DOI: 10.47665/tb.38.1.007
    Chikungunya virus (CHIKV) infection is the cause of acute symptoms and chronic symmetrical polyarthritis associated with long-term morbidity and mortality. Currently, there is no available licensed vaccine or particularly useful drug for human use against CHIKV infection. This study was conducted to evaluate the efficacy of antibodies produced by papaya mosaic virus (PapMV) nanoparticles fused to E2EP3 peptide of CHIKV envelope as a recombinant CHIKV vaccine. PapMV, PapMV-C- E2EP3, and E2EP3-N-PapMV were produced in E. coli with an approximate size of 27 to 30 kDa. ICR mice (5 to 6 weeks of age) were injected subcutaneously with 25 micrograms of vaccine construct, and ELISA measured the titer of CHIKV specific IgG antibodies. The results showed that both recombinant proteins E2EP3-N-PapMV and PapMVC-E2EP3 were able to induce IgG antibodies production in immunized mice against CHIKV while immunization with recombinant PapMV showed no IgG antibodies induction. The neutralizing activity of the antibodies generated by either E2EP3-N-PapMV or PapMV-C-E2EP3 exhibited similar inhibition to CHIKV replication in Vero cells using the cells based antibody neutralizing assay and analyzed by plaque formation assay. This study showed the effectiveness of nanoparticles vaccine generated by fusing epitope peptide of CHIKV envelope to papaya mosaic virus envelope in inducing a robust immune response in mice against CHIKV. The data showed that levels of neutralizing antibodies correlate with a protective immune response CHIKV replication.
    Matched MeSH terms: Chikungunya virus/immunology*
  6. Azlan A, Obeidat SM, Theva Das K, Yunus MA, Azzam G
    PLoS Negl Trop Dis, 2021 01;15(1):e0008351.
    PMID: 33481791 DOI: 10.1371/journal.pntd.0008351
    The Asian tiger mosquito, Aedes albopictus (Ae. albopictus), is an important vector that transmits arboviruses such as dengue (DENV), Zika (ZIKV) and Chikungunya virus (CHIKV). Long noncoding RNAs (lncRNAs) are known to regulate various biological processes. Knowledge on Ae. albopictus lncRNAs and their functional role in virus-host interactions are still limited. Here, we identified and characterized the lncRNAs in the genome of an arbovirus vector, Ae. albopictus, and evaluated their potential involvement in DENV and ZIKV infection. We used 148 public datasets, and identified a total of 10, 867 novel lncRNA transcripts, of which 5,809, 4,139, and 919 were intergenic, intronic and antisense respectively. The Ae. albopictus lncRNAs shared many characteristics with other species such as short length, low GC content, and low sequence conservation. RNA-sequencing of Ae. albopictus cells infected with DENV and ZIKV showed that the expression of lncRNAs was altered upon virus infection. Target prediction analysis revealed that Ae. albopictus lncRNAs may regulate the expression of genes involved in immunity and other metabolic and cellular processes. To verify the role of lncRNAs in virus infection, we generated mutations in lncRNA loci using CRISPR-Cas9, and discovered that two lncRNA loci mutations, namely XLOC_029733 (novel lncRNA transcript id: lncRNA_27639.2) and LOC115270134 (known lncRNA transcript id: XR_003899061.1) resulted in enhancement of DENV and ZIKV replication. The results presented here provide an important foundation for future studies of lncRNAs and their relationship with virus infection in Ae. albopictus.
    Matched MeSH terms: Chikungunya virus
  7. Ananth S, Shrestha N, Treviño C JA, Nguyen US, Haque U, Angulo-Molina A, et al.
    Pathogens, 2020 Nov 19;9(11).
    PMID: 33228120 DOI: 10.3390/pathogens9110964
    Arboviruses such as Chikungunya (CHIKV), Dengue (DENV), and Zika virus (ZIKV) have emerged as a significant public health concern in Mexico. The existing literature lacks evidence regarding the dispersion of arboviruses, thereby limiting public health policy's ability to integrate the diagnosis, management, and prevention. This study seeks to reveal the clinical symptoms of CHIK, DENV, and ZIKV by age group, region, sex, and time across Mexico. The confirmed cases of CHIKV, DENV, and ZIKV were compiled from January 2012 to March 2020. Demographic characteristics analyzed significant clinical symptoms of confirmed cases. Multinomial logistic regression was used to assess the association between clinical symptoms and geographical regions. Females and individuals aged 15 and older had higher rates of reported significant symptoms across all three arboviruses. DENV showed a temporal variation of symptoms by regions 3 and 5, whereas ZIKV presented temporal variables in regions 2 and 4. This study revealed unique and overlapping symptoms between CHIKV, DENV, and ZIKV. However, the differentiation of CHIKV, DENV, and ZIKV is difficult, and diagnostic facilities are not available in rural areas. There is a need for adequately trained healthcare staff alongside well-equipped lab facilities, including hematological tests and imaging facilities.
    Matched MeSH terms: Chikungunya virus
  8. Fazal F, Anwar T, Waheed Y, Parvaiz F
    Trop Biomed, 2020 Sep 01;37(3):566-577.
    PMID: 33612772 DOI: 10.47665/tb.37.3.566
    This study is focused towards developing a global consensus sequence of nonstructural protein 2 (NSP2), a protease of Chikungunya Virus (CHIKV) and predict immunogenic promiscuous T-cell epitopes based on various bioinformatics tools. To date, no epitope data is available for the Chikungunya virus in the IEDB database. In this study, 100 available nucleotide sequences of NSP2-CHIKV belonging to different strains were downloaded from the National Centre for Biotechnology Information (NCBI) database. The nucleotide sequences were subjected to translated sequencing using the EXPASY tool followed by protein alignment using the CLC workbench and a global consensus sequence for the respective protein was developed. IEDB tool was used to predict HLA-I and HLA-II binding promiscuous epitopes from the consensus sequence of NSP2-CHIKV. Thirty-four B-cell based epitopes are predicted and the promiscuous epitope is VVDTTGSTKPDPGD at position 341-354. Twenty-six MHC-I short peptide epitopes are predicted to bind with HLA-A. The promiscuous epitopes predicted to bind with HLA-A*01:01 are VTAIVSSLHY, SLSESATMVY, FSKPLVYY, QPTDHVVGEY at positions 317-326, 84-93, 535-544 and 15-24 with percentile ranks 0.17, 0.39, 0.51 and 0.81, respectively. Twenty-four MHC-II short peptide epitopes are predicted for HLA-DRB. The promiscuous epitope predicted to bind with HLA-DRB*01:01 is VVGEYLVLSPQTVLRS from 20-35 with a lowest percentile rank of 0.01. These predicted epitopes can be effective targets towards development of vaccine against CHIKV. Epitopes predicted in this study displayed good binding affinity, antigenicity and promiscuity for the HLA classes. These predicted epitopes can prove to be translationally important towards the development of CHIKV.
    Matched MeSH terms: Chikungunya virus
  9. Syuhadaratul Aini Mohamat, Nor Fazila Che Mat, Najmo Ibrahim Barkhadle2, Tuan Nur Akmalina Mat Jusoh, Rafidah Hanim Shueb
    MyJurnal
    Chikungunya is an infection caused by chikungunya virus which at present has spread to new countries and con- tinents. Chikungunya is associated with self-limiting and non-fatal infection in the past. However, in recent times, increased severity of the disease has been reported resulting in health and economic burden. The threat and bur- den of chikungunya would grow in future in the absence of specific antiviral or vaccine to control or eliminate the infection. This review discusses chikungunya in general including transmission of its etiological agent and clinical manifestations of the disease. Subsequently, management and treatment of chikungunya virus will be reviewed with particular emphasis on natural products or their active compounds with potential anti-chikungunya virus activities.
    Matched MeSH terms: Chikungunya virus
  10. Suhana O, Nazni WA, Apandi Y, Farah H, Lee HL, Sofian-Azirun M
    Heliyon, 2019 Dec;5(12):e02682.
    PMID: 31867449 DOI: 10.1016/j.heliyon.2019.e02682
    Chikungunya virus (CHIKV) is maintained in the sylvatic cycle in West Africa and is transmitted by Aedes mosquito species to monkeys. In 2006, four verified CHIKV isolates were obtained during a survey of arboviruses in monkeys (Macaca fascicularis) in Pahang state, Peninsular Malaysia. RNA was extracted from the CHIKV isolates and used in reverse transcription polymerase chain reactions (RT-PCR) to amplify PCR fragments for sequencing. Nucleic acid primers were designed to generate overlapping PCR fragments that covered the whole viral sequence. A total of 11,238 base pairs (bp) corresponding to open reading frames (ORFs) from our isolates and 47 other registered isolates in the National Center for Biotechnology Information (NCBI) were used to elucidate sequences, amino acids, and phylogenetic relationships and to estimate divergence times by using MEGA 7.0 and the Bayesian Markov chain Monte Carlo method. Phylogenetic analysis revealed that all CHIKV isolates could be classified into the Asian genotype and clustered with Bagan Panchor clades, which are associated with the chikungunya outbreak reported in 2006, with sequence and amino acid similarities of 99.9% and 99.7%, respectively. Minor amino acid differences were found between human and non-human primate isolates. Amino acid analysis showed a unique amino acid at position 221 in the nsP1region, at which a glycine (G) was found only in monkey isolates, whereas arginine (R) was found at the same position only in human isolates. The time to the most recent common ancestor (MRCA) estimation indicated that CHIKV probably started to diverge from human to non-human primates in approximately 2004 in Malaysia. The results suggested that CHIKV in non-human primates probably resulted from the spillover of the virus from humans. The study will be helpful in understanding the movement and evolution of CHIKV in Malaysia and globally.
    Matched MeSH terms: Chikungunya virus
  11. Fu JYL, Chua CL, Vythilingam I, Sulaiman WYW, Wong HV, Chan YF, et al.
    J Gen Virol, 2019 11;100(11):1541-1553.
    PMID: 31613205 DOI: 10.1099/jgv.0.001338
    Chikungunya virus (CHIKV) has caused large-scale epidemics of fever, rash and arthritis since 2004. This unprecedented re-emergence has been associated with mutations in genes encoding structural envelope proteins, providing increased fitness in the secondary vector Aedes albopictus. In the 2008-2013 CHIKV outbreaks across Southeast Asia, an R82S mutation in non-structural protein 4 (nsP4) emerged early in Malaysia or Singapore and quickly became predominant. To determine whether this nsP4-R82S mutation provides a selective advantage in host cells, which may have contributed to the epidemic, the fitness of infectious clone-derived CHIKV with wild-type nsP4-82R and mutant nsP4-82S were compared in Ae. albopictus and human cell lines. Viral infectivity, dissemination and transmission in Ae. albopictus were not affected by the mutation when the two variants were tested separately. In competition, the nsP4-82R variant showed an advantage over nsP4-82S in dissemination to the salivary glands, but only in late infection (10 days). In human rhabdomyosarcoma (RD) and embryonic kidney (HEK-293T) cell lines coinfected at a 1 : 1 ratio, wild-type nsP4-82R virus was rapidly outcompeted by nsP4-82S virus as early as one passage (3 days). In conclusion, the nsP4-R82S mutation provides a greater selective advantage in human cells than in Ae. albopictus, which may explain its apparent natural selection during CHIKV spread in Southeast Asia. This is an unusual example of a naturally occurring mutation in a non-structural protein, which may have facilitated epidemic transmission of CHIKV.
    Matched MeSH terms: Chikungunya virus/genetics; Chikungunya virus/growth & development*
  12. Malik HAM, Abid F, Mahmood N, Wahiddin MR, Malik A
    Healthc Inform Res, 2019 Jul;25(3):182-192.
    PMID: 31406610 DOI: 10.4258/hir.2019.25.3.182
    Objectives: Dengue epidemic is a dynamic and complex phenomenon that has gained considerable attention due to its injurious effects. The focus of this study is to statically analyze the nature of the dengue epidemic network in terms of whether it follows the features of a scale-free network or a random network.

    Methods: A multifarious network of Aedes aegypti is addressed keeping the viewpoint of a complex system and modelled as a network. The dengue network has been transformed into a one-mode network from a two-mode network by utilizing projection methods. Furthermore, three network features have been analyzed, the power-law, clustering coefficient, and network visualization. In addition, five methods have been applied to calculate the global clustering coefficient.

    Results: It has been observed that dengue epidemic follows a power-law, with the value of its exponent γ = -2.1. The value of the clustering coefficient is high for dengue cases, as weight of links. The minimum method showed the highest value among the methods used to calculate the coefficient. Network visualization showed the main areas. Moreover, the dengue situation did not remain the same throughout the observed period.

    Conclusions: The results showed that the network topology exhibits the features of a scale-free network instead of a random network. Focal hubs are highlighted and the critical period is found. Outcomes are important for the researchers, health officials, and policy makers who deal with arbovirus epidemic diseases. Zika virus and Chikungunya virus can also be modelled and analyzed in this manner.

    Matched MeSH terms: Chikungunya virus
  13. Zarina Mohd Zawawi, Tengku Rogayah Tengku Abdul Rashid, Amir Hussien Adiee, Murni Maya Sari, Ravindran Thayan
    MyJurnal
    Introduction: Dengue virus (DENV), Zika virus (ZIKV) and Chikungunya virus (CHIKV) are Arboviruses that are transmitted by the same vector, Aedes aegypti. Dengue has become a global problem since the Second World War and is common in more than 110 countries. In Malaysia, dengue is a major disease burden as total economic costs to the country as a result of dengue is close to RM1.05 billion in 2010 and estimated to rise to 1.3 billion by 2020. Apart from Dengue, Zika and Chikungunya are the other important mosquito borne diseases in Malaysia. The aim of this study was to develop a multiplex real-time assay for simultaneous detection of DENV, ZIKV and CHIKV in clinical specimens. Methods: The published singleplex protocols were used with key modifications to implement a triplex assay. A one-step multiplex real-time RT-PCR assay was developed that can simultaneously detect RNA of DENV, ZIKV and CHIKV with good performance for a routine diagnostic use. The assay was evaluated for inter- and intra-reproducibility by mean CT value. The diagnostic sensitivity was tested with 135 archived samples which had been defined positive or negative by routine singleplex assays. Whole blood, plasma and urines were used in this study. Results: Intra- and inter-reproducibility and sensitivity varied from 0.10% to 4.73% and from 0.45% to 5.98% for each virus respectively. The specificity of detection was 100%. The multiplex real-time RT-PCR assay showed concordance with test results performed by routine singleplex assays. No cross reaction was observed for any of the clinical samples. Conclusion: The development of a rapid, sensitive and specific molecular assay for DENV, ZIKV and CHIKV infections will produce a greater diagnostic capacity in our laboratory. This multiplex approach is cost effective and robust with the concurrent detection of 3 viruses of public health concern.
    Matched MeSH terms: Chikungunya virus
  14. Tuite AR, Watts AG, Khan K, Bogoch II
    Infect Dis Model, 2019;4:251-256.
    PMID: 31667444 DOI: 10.1016/j.idm.2019.09.001
    Southern Thailand has been experiencing a large chikungunya virus (CHIKV) outbreak since October 2018. Given the magnitude and duration of the outbreak and its location in a popular tourist destination, we sought to determine international case exportation risk and identify countries at greatest risk of receiving travel-associated imported CHIKV cases. We used a probabilistic model to estimate the expected number of exported cases from Southern Thailand between October 2018 and April 2019. The model incorporated data on CHIKV natural history, infection rates in Southern Thailand, average length of stay for tourists, and international outbound air passenger numbers from the outbreak area. For countries highly connected to Southern Thailand by air travel, we ran 1000 simulations to estimate the expected number of imported cases. We also identified destination countries with conditions suitable for autochthonous CHIKV transmission. Over the outbreak period, we estimated that an average of 125 (95% credible interval (CrI): 102-149) cases would be exported from Southern Thailand to international destinations via air travel. China was projected to receive the most cases (43, 95% CrI: 30-56), followed by Singapore (7, 95% CrI: 2-12) and Malaysia (5, 95% CrI: 1-10). Twenty-three countries were projected to receive at least one imported case, and 64% of these countries had one or more regions that could potentially support autochthonous CHIKV transmission. The overall risk of international exportation of CHIKV cases associated with the outbreak is Southern Thailand is high. Our model projections are consistent with recent reports of CHIKV in travelers returning from the region. Countries should be alert to the possibility of CHIKV infection in returning travelers, particularly in regions where autochthonous transmission is possible.
    Matched MeSH terms: Chikungunya virus
  15. Oo A, Rausalu K, Merits A, Higgs S, Vanlandingham D, Bakar SA, et al.
    Antiviral Res, 2018 02;150:101-111.
    PMID: 29269135 DOI: 10.1016/j.antiviral.2017.12.012
    The past decade has seen the re-emergence of Chikungunya virus (CHIKV) as a major global health threat, affecting millions around the world. Although fatal infections are rare among infected patients, the occurrence of long-lasting polyarthralgia has a significant impact on patients' quality of lives and ability to work. These issues were the stimuli for this study to determine the potential of baicalin, a bioflavonoid, as the novel antiviral compound against CHIKV. It was found that baicalin was well tolerated by Vero, BHK-21 and HEK 293T cells with maximal nontoxic doses >600 μM, ≈ 350 μM and ≈110 μM, respectively. Antiviral assays indicated that baicalin was the most effective inhibitor when tested for its direct virucidal activity with EC50 ≈ 7 μM, followed by inhibition of virus entry into the host cell, attachment of virus particle to cellular receptors and finally intracellular replication of viral RNA genome. In silico analysis using molecular docking demonstrated close interactions between baicalin and CHIKV envelope protein with considerably strong binding affinity of -9.7 kcal/mol. qRT-PCR analysis revealed that baicalin had the greatest effect on the synthesis of viral negative stand RNA with EC50 ≈ 0.4 μM followed by the inhibition of synthesis of positive-strand genomic (EC50 ≈ 13 μM) and subgenomic RNAs (EC50 ≈ 14 μM). These readings indicate that the compound efficiently inhibits replicase complexes formation but is a less potent inhibitor of existing replicase complexes. Coherent with this hypothesis, the use of recombinant CHIKV replicons harboring Renilla luciferase marker showed that replication of corresponding replicon RNAs was only slightly downregulated at higher doses of baicalin, with EC50 > 100 μM. Immunofluorescence and western blotting experiments demonstrated dose-dependent inhibition of expression of different viral proteins. It was also observed that levels of important protein markers for cellular autophagy (LC3) and apoptosis (Bax) were reduced in baicalin treatment groups as compared with untreated virus infected controls. In summary, given its low toxicity and high efficacy against CHIKV, baicalin has great potential to be developed as the novel antiviral compound for CHIKV. In vivo studies to evaluate its activity in a more complexed system represent a necessary step for future analysis.
    Matched MeSH terms: Chikungunya virus/drug effects*
  16. Nakayama E, Tajima S, Kotaki A, Shibasaki KI, Itokawa K, Kato K, et al.
    J Travel Med, 2018 01 01;25(1).
    PMID: 29394382 DOI: 10.1093/jtm/tax072
    Background: Due to the huge 2-way human traffic between Japan and Chikungunya (CHIK) fever-endemic regions, 89 imported cases of CHIK fever were confirmed in Japan from January 2006 to June 2016. Fifty-four of 89 cases were confirmed virologically and serologically at the National Institute of Infectious Diseases, Japan and we present the demographic profiles of the patients and the phylogenetic features of 14 CHIK virus (CHIKV) isolates.

    Methods: Patients were diagnosed with CHIK fever by a combination of virus isolation, viral RNA amplification, IgM antibody-, IgG antibody-, and/or neutralizing antibody detection. The whole-genome sequences of the CHIKV isolates were determined by next-generation sequencing.

    Results: Prior to 2014, the source countries of the imported CHIK fever cases were limited to South and Southeast Asian countries. After 2014, when outbreaks occurred in the Pacific and Caribbean Islands and Latin American countries, there was an increase in the number of imported cases from these regions. A phylogenetic analysis of 14 isolates revealed that four isolates recovered from three patients who returned from Sri Lanka, Malaysia and Angola, belonged to the East/Central/South African genotype, while 10 isolates from 10 patients who returned from Indonesia, the Philippines, Tonga, the Commonwealth of Dominica, Colombia and Cuba, belonged to the Asian genotype.

    Conclusion: Through the phylogenetic analysis of the isolates, we could predict the situations of the CHIK fever epidemics in Indonesia, Angola and Cuba. Although Japan has not yet experienced an autochthonous outbreak of CHIK fever, the possibility of the future introduction of CHIKV through an imported case and subsequent local transmission should be considered, especially during the mosquito-active season. The monitoring and reporting of imported cases will be useful to understand the situation of the global epidemic, to increase awareness of and facilitate the diagnosis of CHIK fever, and to identify a future CHIK fever outbreak in Japan.

    Matched MeSH terms: Chikungunya virus/isolation & purification*
  17. Dzaki N, Azzam G
    PLoS One, 2018;13(3):e0194664.
    PMID: 29554153 DOI: 10.1371/journal.pone.0194664
    Members of the Aedes genus of mosquitoes are widely recognized as vectors of viral diseases. Ae.albopictus is its most invasive species, and are known to carry viruses such as Dengue, Chikugunya and Zika. Its emerging importance puts Ae.albopictus on the forefront of genetic interaction and evolution studies. However, a panel of suitable reference genes specific for this insect is as of now undescribed. Nine reference genes, namely ACT, eEF1-γ, eIF2α, PP2A, RPL32, RPS17, PGK1, ILK and STK were evaluated. Expression patterns of the candidate reference genes were observed in a total of seventeen sample types, separated by stage of development and age. Gene stability was inferred from obtained quantification data through three widely cited evaluation algorithms i.e. BestKeeper, geNorm, and NormFinder. No single gene showed a satisfactory degree of stability throughout all developmental stages. Therefore, we propose combinations of PGK and ILK for early embryos; RPL32 and RPS17 for late embryos, all four larval instars, and pupae samples; eEF1-γ with STK for adult males; eEF1-γ with RPS17 for non-blood fed females; and eEF1-γ with eIF2α for both blood-fed females and cell culture. The results from this study should be able to provide a more informed selection of normalizing genes during qPCR in Ae.albopictus.
    Matched MeSH terms: Chikungunya virus/genetics
  18. Yap ML, Klose T, Urakami A, Hasan SS, Akahata W, Rossmann MG
    Proc Natl Acad Sci U S A, 2017 12 26;114(52):13703-13707.
    PMID: 29203665 DOI: 10.1073/pnas.1713166114
    Cleavage of the alphavirus precursor glycoprotein p62 into the E2 and E3 glycoproteins before assembly with the nucleocapsid is the key to producing fusion-competent mature spikes on alphaviruses. Here we present a cryo-EM, 6.8-Å resolution structure of an "immature" Chikungunya virus in which the cleavage site has been mutated to inhibit proteolysis. The spikes in the immature virus have a larger radius and are less compact than in the mature virus. Furthermore, domains B on the E2 glycoproteins have less freedom of movement in the immature virus, keeping the fusion loops protected under domain B. In addition, the nucleocapsid of the immature virus is more compact than in the mature virus, protecting a conserved ribosome-binding site in the capsid protein from exposure. These differences suggest that the posttranslational processing of the spikes and nucleocapsid is necessary to produce infectious virus.
    Matched MeSH terms: Chikungunya virus/metabolism; Chikungunya virus/ultrastructure*; Chikungunya virus/chemistry*
  19. Ehteshami M, Tao S, Zandi K, Hsiao HM, Jiang Y, Hammond E, et al.
    PMID: 28137799 DOI: 10.1128/AAC.02395-16
    Chikungunya virus (CHIKV) represents a reemerging global threat to human health. Recent outbreaks across Asia, Europe, Africa, and the Caribbean have prompted renewed scientific interest in this mosquito-borne alphavirus. There are currently no vaccines against CHIKV, and treatment has been limited to nonspecific antiviral agents, with suboptimal outcomes. Herein, we have identified β-d-N4-hydroxycytidine (NHC) as a novel inhibitor of CHIKV. NHC behaves as a pyrimidine ribonucleoside and selectively inhibits CHIKV replication in cell culture.
    Matched MeSH terms: Chikungunya virus/drug effects*
  20. Ahmad NA, Vythilingam I, Lim YAL, Zabari NZAM, Lee HL
    Am J Trop Med Hyg, 2017 Jan 11;96(1):148-156.
    PMID: 27920393 DOI: 10.4269/ajtmh.16-0516
    Wolbachia-based vector control strategies have been proposed as a means to augment the currently existing measures for controlling dengue and chikungunya vectors. Prior to utilizing Wolbachia as a novel vector control strategy, it is crucial to understand the Wolbachia-mosquito interactions. In this study, field surveys were conducted to screen for the infection status of Wolbachia in field-collected Aedes albopictus The effects of Wolbachia in its native host toward the replication and dissemination of chikungunya virus (CHIKV) was also studied. The prevalence of Wolbachia-infected field-collected Ae. albopictus was estimated to be 98.6% (N = 142) for females and 95.1% (N = 102) for males in the population studied. The Ae. albopictus were naturally infected with both wAlbA and wAlbB strains. We also found that the native Wolbachia has no impact on CHIKV infection and minimal effect on CHIKV dissemination to secondary organs.
    Matched MeSH terms: Chikungunya virus/isolation & purification*
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