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Special Issue "Chikungunya Virus and Emerging Alphaviruses"

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Published Papers

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (1 August 2023) | Viewed by 26519

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Special Issue Editors

Dr. Rafael Freitas de Oliveira Franca

E-Mail Website
Guest Editor

Oswaldo Cruz Foundation/Fiocruz, Aggeu Magalhães Institute, Recife 50740-465, Brazil
Interests: positive-strand RNA Zika virus; Chikungunya; Dengue virus; pathogenesis

Dr. Sergio de Paula

E-Mail Website
Guest Editor

Molecular Immunovirology Laboratory, General Biology Department, Universidade Federal de Viçosa, Viçosa, MG 36570-900, Brazil
Interests: virus genomes; dengue virus; SARS-COV-2; Zika virus; Mayaro virus; vaccine development; molecular diagnosis; bacteriophages; heterologous protein expression

Special Issue Information

Dear Colleagues,

Chikungunya virus (CHIKV) is a re-emerging arthropod-borne virus that is widespread in tropical regions. This virus belongs to the Alphavirus genus and is transmitted to humans by the bite of Aedes spp.-infected mosquitoes, a vector commonly found in many large cities. CHIKV has an immense impact on global public health, especially in middle- and low-income countries, in which access to health is limited. Chikungunya infection is usually characterized by an abrupt onset of fever, which is commonly followed by significant joint pain. Chikungunya virus-induced joint pain is often a very debilitating symptom, lasting from a few days to several weeks or even months. Other symptoms, such as atypical neurological manifestations, have also been reported; these include meningo-encephalitis, meningoencephalo-myeloradiculitis, myeloradiculitis, myelitis, myeloneuropathy, and Guillain–Barré syndrome. Besides CHIKV, other important Alphaviruses (Mayaro, Ross River, and Venezuelan equine encephalitis, among others) can cause human disease. Despite its importance, at the present no treatment or vaccines are available to control Alphavirus infections.

Although there have been significant advances in science—such as, for instance, the implementation of novel mRNA vaccines—new emerging and re-emerging viruses still represent a major challenge to the field. For this Special Issue, we welcome the submission of original research articles, review articles, and short communications that contribute to an improved understanding of Alphaviruses. Topics of interest include, but are not limited to:

- Alphaviruses epidemiology and virus surveillance (emergence and virus evolution);
- Advances in diagnostics, treatment, and vaccines;
- Basic virology molecular aspects;
- Alphaviruses pathogenesis (including, but not limited to, host response and host factors affecting infection outcomes, animal models of infection, host innate and adaptive immunity, virus immune response evasion);
- Measures for control and prevention.

Dr. Rafael Freitas de Oliveira Franca
Dr. Sergio de Paula
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

chikungunya virus
alphavirus
innate immune response
adaptive immune response
epidemiology
diagnosis
prevention
vaccine
animal model
pathogenesis
viral evolution
in vitro
in vivo
mayaro virus
ross river virus
semliki forest virus
venezuelan equine encephalitis virus

Published Papers (17 papers)

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Editorial

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Open AccessEditorial

Special Issue “Chikungunya Virus and Emerging Alphaviruses”

Mylena R. Pereira

and

Rafael F. O. Franca

Viruses 2023, 15(8), 1768; https://doi.org/10.3390/v15081768 - 19 Aug 2023

Viewed by 550

Abstract

Chikungunya virus (CHIKV), an alphavirus transmitted by mosquitoes, has experienced a recent re-emergence in various regions of the world, leading to large-scale outbreaks [...] Full article

(This article belongs to the Special Issue Chikungunya Virus and Emerging Alphaviruses)

Research

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Open AccessArticle

Mapping Eastern (EEE) and Venezuelan Equine Encephalitides (VEE) among Equines Using Geographical Information Systems, Colombia, 2008–2019

D. Katterine Bonilla-Aldana

Christian David Bonilla Carvajal

Emilly Moreno-Ramos

Joshuan J. Barboza

and

Alfonso J. Rodriguez-Morales

Viruses 2023, 15(3), 707; https://doi.org/10.3390/v15030707 - 08 Mar 2023

Cited by 1 | Viewed by 1169

Abstract

Introduction: Eastern equine encephalitis virus (EEEV) and Venezuelan equine encephalitis virus (VEEV) viruses are zoonotic pathogens affecting humans, particularly equines. These neuroarboviruses compromise the central nervous system and can be fatal in different hosts. Both have significantly influenced Colombia; however, few studies analyse its behaviour, and none develop maps using geographic information systems to characterise it. Objective: To describe the temporal-spatial distribution of those viruses in Colombia between 2008 and 2019. Methods: Retrospective cross-sectional descriptive study, based on weekly reports by municipalities of the ICA, of the surveillance of both arboviruses in equines, in Colombia, from 2008 to 2019. The data were converted into databases in Microsoft Access 365^®, and multiple epidemiological maps were generated with the Kosmo RC1^®3.0 software coupled to shape files of all municipalities in the country. Results: In the study period, 96 cases of EEE and 70 of VEE were reported, with 58% of EEE cases occurring in 2016 and 20% of EEV cases in 2013. The most affected municipalities for EEE corresponded to the department of Casanare: Yopal (20), Aguazul (16), and Tauramena (10). In total, 40 municipalities in the country reported ≥1 case of EEE. Conclusions: The maps allow a quick appreciation of groups of neighbouring municipalities in different departments (1° political division) and regions of the country affected by those viruses, which helps consider the expansion of the disease associated with mobility and transport of equines between other municipalities, also including international borders, such as is the case with Venezuela. In that country, especially for EEV, municipalities in the department of Cesar are bordering and at risk for that arboviral infection. there is a high risk of equine encephalitis outbreaks, especially for VEE. This poses a risk also, for municipalities in the department of Cesar, bordering with Venezuela. Full article

(This article belongs to the Special Issue Chikungunya Virus and Emerging Alphaviruses)

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Open AccessArticle

Deubiquitinating Enzyme Inhibitors Block Chikungunya Virus Replication

Lady S. López

Eliana P. Calvo

and

Jaime E. Castellanos

Viruses 2023, 15(2), 481; https://doi.org/10.3390/v15020481 - 09 Feb 2023

Cited by 1 | Viewed by 1439

Abstract

Ubiquitination and deubiquitination processes are widely involved in modulating the function, activity, localization, and stability of multiple cellular proteins regulating almost every aspect of cellular function. Several virus families have been shown to exploit the cellular ubiquitin-conjugating system to achieve a productive infection: enter the cell, promote genome replication, or assemble and release viral progeny. In this study, we analyzed the role of deubiquitinating enzymes (DUBs) during chikungunya virus (CHIKV) infection. HEK293T, Vero-E6, and Huh-7 cells were treated with two DUB inhibitors (PR619 or WP1130). Then, infected cells were evaluated by flow cytometry, and viral progeny was quantified using the plaque assay method. The changes in viral proteins and viral RNA were analyzed using Western blotting and RT-qPCR, respectively. Results indicate that treatment with DUB inhibitors impairs CHIKV replication due to significant protein and viral RNA synthesis deregulation. Therefore, DUB activity may be a pharmacological target for blocking CHIKV infection. Full article

(This article belongs to the Special Issue Chikungunya Virus and Emerging Alphaviruses)

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Open AccessArticle

Nanomechanical and Vibrational Signature of Chikungunya Viral Particles

Ruana Cardoso-Lima

Joel Félix Silva Diniz Filho

Maria Luiza de Araujo Dorneles

Renato Simões Gaspar

Pedro Filho Noronha Souza

Clenilton Costa dos Santos

Daniela Santoro Rosa

Ralph Santos-Oliveira

and

Luciana Magalhães Rebelo Alencar

Viruses 2022, 14(12), 2821; https://doi.org/10.3390/v14122821 - 17 Dec 2022

Cited by 2 | Viewed by 1217

Abstract

Chikungunya virus (CHIKV) belongs to the genus Alphaviridae, with a single-stranded positive-sense RNA genome of 11.8 kbp encoding a polyprotein that generates both non-structural proteins and structural proteins. The virus is transmitted by the Aedes aegypti and A. albopictus mosquitoes, depending on the location. CHIKV infection leads to dengue-like musculoskeletal symptoms and has been responsible for several outbreaks worldwide since its discovery in 1952. Patients often experience fever, headache, muscle pain, joint swelling, and skin rashes. However, the ultrastructural and mechanical properties of CHIKV have not been fully characterized. Thus, this study aims to apply a physical approach to investigate CHIKV′s ultrastructural morphology and mechanical properties, using atomic force microscopy and Raman spectroscopy as the main tools. Using nanomechanical assays of AFM and a gold nanoparticles substrate for Raman signal enhancement, we explored the conformational plasticity, morphology, vibrational signature, and nanomechanical properties of the chikungunya virus, providing new information on its ultrastructure at the nanoscale and offering a novel understanding of the virus’ behavior upon mechanical disruptions besides its molecular composition. Full article

(This article belongs to the Special Issue Chikungunya Virus and Emerging Alphaviruses)

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Open AccessArticle

Cell-Type-Dependent Role for nsP3 Macrodomain ADP-Ribose Binding and Hydrolase Activity during Chikungunya Virus Infection

and

Viruses 2022, 14(12), 2744; https://doi.org/10.3390/v14122744 - 09 Dec 2022

Cited by 1 | Viewed by 1085

Abstract

Chikungunya virus (CHIKV) causes outbreaks of rash, arthritis, and fever associated with neurologic complications, where astrocytes are preferentially infected. A determinant of virulence is the macrodomain (MD) of nonstructural protein 3 (nsP3), which binds and removes ADP-ribose (ADPr) from ADP-ribosylated substrates and regulates stress-granule disruption. We compared the replication of CHIKV 181/25 (WT) and MD mutants with decreased ADPr binding and hydrolase (G32S) or increased ADPr binding and decreased hydrolase (Y114A) activities in C8-D1A astrocytic cells and NSC-34 neuronal cells. WT CHIKV replication was initiated more rapidly with earlier nsP synthesis in C8-D1A than in NSC-34 cells. G32S established infection, amplified replication complexes, and induced host-protein synthesis shut-off less efficiently than WT and produced less infectious virus, while Y114A replication was close to WT. However, G32S mutation effects on structural protein synthesis were cell-type-dependent. In NSC-34 cells, E2 synthesis was decreased compared to WT, while in C8-D1A cells synthesis was increased. Excess E2 produced by G32S-infected C8-D1A cells was assembled into virus particles that were less infectious than those from WT or Y114A-infected cells. Because nsP3 recruits ADP-ribosylated RNA-binding proteins in stress granules away from translation-initiation factors into nsP3 granules where the MD hydrolase can remove ADPr, we postulate that suboptimal translation-factor release decreased structural protein synthesis in NSC-34 cells while failure to de-ADP-ribosylate regulatory RNA-binding proteins increased synthesis in C8-D1A cells. Full article

(This article belongs to the Special Issue Chikungunya Virus and Emerging Alphaviruses)

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Open AccessArticle

Assessment of Dengue and Chikungunya Infections among Febrile Patients Visiting Four Healthcare Centres in Yaoundé and Dizangué, Cameroon

Stella Mariette Nana-Ndjangwo

Borel Djiappi-Tchamen

Ruth Mony

Maurice Demanou

Joyce Keumezeu-Tsafack

Roland Bamou

Parfait Awono-Ambene

Charles Félix Bilong Bilong

and

Christophe Antonio-Nkondjio

Viruses 2022, 14(10), 2127; https://doi.org/10.3390/v14102127 - 27 Sep 2022

Cited by 3 | Viewed by 1279

Abstract

Dengue and chikungunya are now widely distributed in Cameroon, but there is still not enough information on their prevalence in different epidemiological settings. This study was undertaken to assess the prevalence of dengue and chikungunya in both urban and rural settings in Cameroon using three diagnostic tools. From December 2019 to September 2021, willing febrile (temperature >38 °C) outpatients visiting four healthcare facilities in the cities of Yaoundé and Dizangué were screened for dengue, and chikungunya. Clinical features of patient were recorded in a form, and their blood samples were analysed using real-time reverse transcriptase-polymerase chain reaction (rtRT-PCR), rapid diagnostic tests (RDTs) and enzyme-linked immuno-sorbent assays (ELISA). Odds ratios were used to determine the level of association between socio-demographic factors, clinical features, and infection status. The Kappa coefficient permitted to assess the level of agreement between RDTs and ELISA. Overall, 301 febrile patients were recruited in the study: 198 in Yaoundé and 103 in Dizangué. The prevalence of infection varied with the diagnostic tool used. For dengue diagnostics, 110 patients were positive to rtRT-PCR: 90 (45.45%) in Yaoundé, and 20 (19.42%) in Dizangué. The prevalence of dengue IgM using ELISA varied from 22.3% in Dizangué to 30.8% in Yaoundé. Dengue IgM rate using RDTs was 7.6% in Yaoundé and 3.9% in Dizangué. For chikungunya, one (0.5%) patient (Yaoundé, suburb) was positive to rtRT-PCR. The prevalence of chikungunya IgM according to ELISA varied from 18.4% in Dizangué to 21.7% in Yaoundé, while it was 4.5% in Yaoundé and 12.6% in Dizangué with RDTs. Only abdominal and retro-orbital pains were significantly associated with acute dengue infection. All four dengue serotypes were recorded, with a predominance of DENV-3 (35.45%) and DENV-4 (25.45%). Rapid Diagnostic Tests for either chikungunya or dengue displayed very poor sensitivity. This study further confirms the high endemicity of both dengue and chikungunya in Yaoundé and Dizangué. These data stress the need for active surveillance and the implementation of vector control measures to prevent the occurrence of outbreaks across the country. Full article

(This article belongs to the Special Issue Chikungunya Virus and Emerging Alphaviruses)

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Open AccessArticle

In Depth Viral Diversity Analysis in Atypical Neurological and Neonatal Chikungunya Infections in Rio de Janeiro, Brazil

and

Ana Maria Bispo de Filippis

Viruses 2022, 14(9), 2006; https://doi.org/10.3390/v14092006 - 10 Sep 2022

Cited by 2 | Viewed by 1281

Abstract

Chikungunya virus (CHIKV) is an arthropod-borne virus (arbovirus) transmitted by Aedes mosquitoes. The human infection usually manifests as a febrile and incapacitating arthritogenic illness, self-limiting and non-lethal. However, since 2013, CHIKV spreading through the tropics and to the Americas was accompanied by an increasing number of cases of atypical disease presentation, namely severe neuropathies and neonatal infection due to intrapartum vertical transmission. The pathophysiological mechanisms underlying these conditions have not been fully elucidated. However, arbovirus intrahost genetic diversity is thought to be linked to viral pathogenesis. To determine whether particular viral variants could be somehow associated, we analyzed the intrahost genetic diversity of CHIKV in three infected patients with neurological manifestations and three mothers infected during the intrapartum period, as well as their babies following vertical transmission. No statistically supported differences were observed for the genetic variability (nucleotide substitutions/gene length) along the genome between the groups. However, the newborn and cerebrospinal fluid samples (corresponding to virus passed through the placenta and/or the blood–brain barrier (BBB)) presented a different composition of their intrahost mutant ensembles compared to maternal or patient serum samples, even when concurrent. This finding could be consistent with the unidirectional virus transmission through these barriers, and the effect of selective bottlenecks during the transmission event. In addition, a higher proportion of defective variants (insertions/deletions and stop codons) was detected in the CSF and maternal samples and those were mainly distributed within the viral non-structural genes. Since defective viral genomes in RNA viruses are known to contribute to the outcome of acute viral infections and influence disease severity, their role in these atypical cases should be further investigated. Finally, with the in silico approach adopted, we detected no relevant non-conservative mutational pattern that could provide any hint of the pathophysiological mechanisms underlying these atypical cases. The present analysis represents a unique contribution to our understanding of the transmission events in these cases and generates hypotheses regarding underlying mechanisms, that can be explored further. Full article

(This article belongs to the Special Issue Chikungunya Virus and Emerging Alphaviruses)

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Open AccessCommunication

Viral Metagenomics for the Identification of Emerging Infections in Clinical Samples with Inconclusive Dengue, Zika, and Chikungunya Viral Amplification

Juliana Vanessa Cavalcante Souza

Hazerral de Oliveira Santos

Anderson Brandão Leite

Marta Giovanetti

Rafael dos Santos Bezerra

Eneas de Carvalho

Jardelina de Souza Todão Bernardino

Vincent Louis Viala

Rodrigo Haddad

Massimo Ciccozzi

Luiz Carlos Junior Alcantara

Sandra Coccuzzo Sampaio

Dimas Tadeu Covas

Simone Kashima

Maria Carolina Elias

and

Svetoslav Nanev Slavov

Viruses 2022, 14(9), 1933; https://doi.org/10.3390/v14091933 - 31 Aug 2022

Cited by 2 | Viewed by 1552

Abstract

Viral metagenomics is increasingly being used for the identification of emerging and re-emerging viral pathogens in clinical samples with unknown etiology. The objective of this study was to shield light on the metavirome composition in clinical samples obtained from patients with clinical history compatible with an arboviral infection, but that presented inconclusive results when tested using RT-qPCR. The inconclusive amplification results might be an indication of the presence of an emerging arboviral agent that is inefficiently amplified by conventional PCR techniques. A total of eight serum samples with inconclusive amplification results for the routinely tested arboviruses—dengue (DENV), Zika (ZIKV), and Chikungunya (CHIKV) obtained during DENV and CHIKV outbreaks registered in the state of Alagoas, Northeast Brazil between July and August 2021—were submitted to metagenomic next-generation sequencing assay using NextSeq 2000 and bioinformatic pipeline for viral discovery. The performed bioinformatic analysis revealed the presence of two arboviruses: DENV type 2 (DENV-2) and CHIKV with a high genome coverage. Further, the metavirome of those samples revealed the presence of multiple commensal viruses apparently without clinical significance. The phylogenetic analysis demonstrated that the DENV-2 genome belonged to the Asian/American genotype and clustered with other Brazilian strains. The identified CHIKV genome was taxonomically assigned as ECSA genotype, which is circulating in Brazil. Together, our results reinforce the utility of metagenomics as a valuable tool for viral identification in samples with inconclusive arboviral amplification. Viral metagenomics is one of the most potent methods for the identification of emerging arboviruses. Full article

(This article belongs to the Special Issue Chikungunya Virus and Emerging Alphaviruses)

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Open AccessArticle

Pro-Inflammatory Profile of Children Exposed to Maternal Chikungunya Virus Infection during the Intrauterine Period: A One-Year Follow-Up Study

Renan Faustino

Fabiana Rabe Carvalho

Thalia Medeiros

Débora Familiar-Macedo

Renata Artimos de Oliveira Vianna

Paulo Emílio Côrrea Leite

Isabela Resende Pereira

Claudete Aparecida Araújo Cardoso

Elzinandes Leal De Azeredo

and

Andrea Alice Silva

Viruses 2022, 14(9), 1881; https://doi.org/10.3390/v14091881 - 26 Aug 2022

Cited by 1 | Viewed by 1148

Abstract

Chikungunya virus (CHIKV) vertical transmission occurs due to maternal viremia in the prepartum. Clinical presentation in neonates can be varied; however, the consequences of intrauterine exposure on the immune response are unclear. Thus, we aimed to analyze inflammatory alterations in children exposed to maternal CHIKV infection. This is a cross-sectional study that included children exposed to maternal CHIKV infection (confirmed by RT-qPCR and/or IgM). Circulant immune mediators were analyzed by a multiplex assay. RESULTS: We included 33 children, with a mean age of 3 ± 2.9 months-old, and 19 (57.6%) were male. Only one child presented neurological alterations. CHIKV-exposed infants showed elevated levels of MIP-1α, MIP-1β, and CCL-2 (p < 0.05). Pro-inflammatory cytokines such as TNFα, IL-6, and IL-7 (p < 0.0001) were also increased. In addition, lower levels of PDGF-BB and GM-CSF were observed in the same group (p < 0.0001). Principal component (PC) analysis highlighted a distinction in the inflammatory profile between groups, where PC explained 56.6% of the alterations. Our findings suggest that maternal exposure to CHIKV can affect the circulating levels of pro-inflammatory cytokines during the infants’ first year of life. The long-term clinical consequences of these findings should be investigated. Full article

(This article belongs to the Special Issue Chikungunya Virus and Emerging Alphaviruses)

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Open AccessCommunication

Chikungunya Virus Shedding in Semen: A Case Series

Ezequias B. Martins

Fernanda de Bruycker-Nogueira

Cintia D. S. Rodrigues

Carolina C. Santos

Simone A. Sampaio

Allison A. Fabri

Vinícius Guerra-Campos

Maria Angélica M. Mares-Guia

Isabella C. V. Moraes

Anielle Pina-Costa

Ana Maria B. Filippis

Patrícia Brasil

and

Guilherme A. Calvet

Viruses 2022, 14(9), 1879; https://doi.org/10.3390/v14091879 - 26 Aug 2022

Cited by 2 | Viewed by 1203

Abstract

Background: Chikungunya is a viral disease that is transmitted by mosquitoes. It is characterized by an acute onset of fever and severe arthralgia. Methods: We describe six cases of acute and post-acute chikungunya in which viral RNA was detected in semen. Conclusions: The most prolonged detection period was 56 days after illness onset. We attempted to cultivate positive semen samples, but virus isolation was unsuccessful in all cases. Full article

(This article belongs to the Special Issue Chikungunya Virus and Emerging Alphaviruses)

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Open AccessArticle

Virological, Serological and Clinical Analysis of Chikungunya Virus Infection in Thai Patients

Yin May Tun

Prakaykaew Charunwatthana

Nathamon Kosoltanapiwat

Passanesh Sukphopetch

and

Kobporn Boonnak

Viruses 2022, 14(8), 1805; https://doi.org/10.3390/v14081805 - 18 Aug 2022

Cited by 4 | Viewed by 1320

Abstract

From 2018 to 2020, the Chikungunya virus (CHIKV) outbreak re-emerged in Thailand with a record of more than 10,000 cases up until the end of 2020. Here, we studied acute CHIKV-infected patients who had presented to the Bangkok Hospital for Tropical Diseases from 2019 to 2020 by assessing the relationship between viral load, clinical features, and serological profile. The results from our study showed that viral load was significantly high in patients with fever, headache, and arthritis. We also determined the neutralizing antibody titer in response to the viral load in patients, and our data support the evidence that an effective neutralizing antibody response against the virus is important for control of the viral load. Moreover, the phylogenetic analysis revealed that the CHIKV strains we studied belonged to the East, Central, and Southern African (ECSA) genotype, of the Indian ocean lineage (IOL), and possessed E1-K211E and E1-I317V mutations. Thus, this study provides insight for a better understanding of CHIKV pathogenesis in acute infection, along with the genomic diversity of the current CHIKV strains circulating in Thailand. Full article

(This article belongs to the Special Issue Chikungunya Virus and Emerging Alphaviruses)

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Open AccessCommunication

Construction and Evaluation of Recombinant Adenovirus Candidate Vaccines for Chikungunya Virus

and

Viruses 2022, 14(8), 1779; https://doi.org/10.3390/v14081779 - 15 Aug 2022

Cited by 1 | Viewed by 1067

Abstract

Chikungunya virus (CHIKV) is a mosquito-borne virus. The emergence of CHIKV infection has raised global concern, and there is a growing need to develop safe and effective vaccines. Here, adenovirus 5 was used as the vaccine vector to construct recombinant adenoviruses expressing CHIKV E2, E1, and E2-6K-E1, respectively. And then the immunogenicity and protective efficiency against CHIKV were evaluated in BALB/c mice. Compared to the ad-wt control group, all three vaccines elicited significant humoral and cellar immune responses. The levels of neutralizing antibodies in the rAd-CHIKV-E2-6K-E1 and rAd-CHIKV-E2 groups both reached 1:256, which were 3.2 times higher than those in the rAd-CHIKV-E1 group. Furthermore, the levels of lymphocyte proliferation in rAd-CHIKV-E2-6K-E1 group were the highest. Besides, the concentrations of IFN-γ and IL-4 in mice immunized with rAd-CHIKV-E2-6K-E1 were 1.37 and 1.20 times higher than those in ad-wt immunized mice, respectively. After the challenge, mice in the rAd-CHIKV-E2-6K-E1 and rAd-CHIKV-E2 groups lost 2% of their body weight compared with 5% in the ad-wt control group. And low viral loads were detected in the heart, kidney, and blood of mice immunized with rAd-CHIKV-E2-6K-E1 and rAd-CHIKV-E2 at 3–5 dpc, which decreased by 0.4–0.7 orders of magnitude compared with the ad-wt control. Overall, these data suggest that the recombinant adenovirus is a potential candidate vaccine against CHIKV. Full article

(This article belongs to the Special Issue Chikungunya Virus and Emerging Alphaviruses)

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Open AccessArticle

Chikungunya Virus Asian Lineage Infection in the Amazon Region Is Maintained by Asiatic and Caribbean-Introduced Variants

Geovani de Oliveira Ribeiro

Danielle Elise Gill

Endrya do Socorro Foro Ramos

Fabiola Villanova

Edcelha Soares D’Athaide Ribeiro

Fred Julio Costa Monteiro

Vanessa S. Morais

Marlisson Octavio da S. Rego

Emerson Luiz Lima Araújo

Antonio Charlys da Costa

and

Élcio Leal

Viruses 2022, 14(7), 1445; https://doi.org/10.3390/v14071445 - 30 Jun 2022

Cited by 2 | Viewed by 1477

Abstract

The simultaneous transmission of two lineages of the chikungunya virus (CHIKV) was discovered after the pathogen’s initial arrival in Brazil. In Oiapoque (Amapá state, north Brazil), the Asian lineage (CHIKV-Asian) was discovered, while in Bahia state, the East-Central-South-African lineage (CHIKV-ECSA) was discovered (northeast Brazil). Since then, the CHIKV-Asian lineage has been restricted to the Amazon region (mostly in the state of Amapá), whereas the ECSA lineage has expanded across the country. Despite the fact that the Asian lineage was already present in the Amazon region, the ECSA lineage brought from the northeast caused a large outbreak in the Amazonian state of Roraima (north Brazil) in 2017. Here, CHIKV spread in the Amazon region was studied by a Zika–Dengue–Chikungunya PCR assay in 824 serum samples collected between 2013 and 2016 from individuals with symptoms of viral infection in the Amapá state. We found 11 samples positive for CHIKV-Asian, and, from these samples, we were able to retrieve 10 full-length viral genomes. A comprehensive phylogenetic study revealed that nine CHIKV sequences came from a local transmission cluster related to Caribbean strains, whereas one sequence was related to sequences from the Philippines. These findings imply that CHIKV spread in different ways in Roraima and Amapá, despite the fact that both states had similar climatic circumstances and mosquito vector frequencies. Full article

(This article belongs to the Special Issue Chikungunya Virus and Emerging Alphaviruses)

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Review

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Open AccessReview

Mayaro Virus: The State-of-the-Art for Antiviral Drug Development

Ana Paula Andreolla

Alessandra Abel Borges

Juliano Bordignon

and

Claudia Nunes Duarte dos Santos

Viruses 2022, 14(8), 1787; https://doi.org/10.3390/v14081787 - 16 Aug 2022

Cited by 4 | Viewed by 1736

Abstract

Mayaro virus is an emerging arbovirus that causes nonspecific febrile illness or arthralgia syndromes similar to the Chikungunya virus, a virus closely related from the Togaviridae family. MAYV outbreaks occur more frequently in the northern and central-western states of Brazil; however, in recent years, virus circulation has been spreading to other regions. Due to the undifferentiated initial clinical symptoms between MAYV and other endemic pathogenic arboviruses with geographic overlapping, identification of patients infected by MAYV might be underreported. Additionally, the lack of specific prophylactic approaches or antiviral drugs limits the pharmacological management of patients to treat symptoms like pain and inflammation, as is the case with most pathogenic alphaviruses. In this context, this review aims to present the state-of-the-art regarding the screening and development of compounds/molecules which may present anti-MAYV activity and infection inhibition. Full article

(This article belongs to the Special Issue Chikungunya Virus and Emerging Alphaviruses)

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Open AccessReview

Chikungunya Immunopathology as It Presents in Different Organ Systems

Elizabeth M. Traverse

and

Viruses 2022, 14(8), 1786; https://doi.org/10.3390/v14081786 - 16 Aug 2022

Cited by 2 | Viewed by 1686

Abstract

Chikungunya virus (CHIKV) is currently an urgent public health problem as high morbidity from the virus leaves populations with negative physical, social, and economic impacts. CHIKV has the potential to affect every organ of an individual, leaving patients with lifelong impairments which negatively affect their quality of life. In this review, we show the importance of CHIKV in research and public health by demonstrating the immunopathology of CHIKV as it presents in different organ systems. Papers used in this review were found on PubMed, using “chikungunya and [relevant organ system]”. There is a significant inflammatory response during CHIKV infection which affects several organ systems, such as the brain, heart, lungs, kidneys, skin, and joints, and the immune response to CHIKV in each organ system is unique. Whilst there is clinical evidence to suggest that serious complications can occur, there is ultimately a lack of understanding of how CHIKV can affect different organ systems. It is important for clinicians to understand the risks to their patients. Full article

(This article belongs to the Special Issue Chikungunya Virus and Emerging Alphaviruses)

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Open AccessReview

A Review on Chikungunya Virus Epidemiology, Pathogenesis and Current Vaccine Development

Thaise Yasmine Vasconcelos de Lima Cavalcanti

Mylena Ribeiro Pereira

Sergio Oliveira de Paula

and

Rafael Freitas de Oliveira Franca

Viruses 2022, 14(5), 969; https://doi.org/10.3390/v14050969 - 05 May 2022

Cited by 27 | Viewed by 4247

Abstract

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that recently re-emerged in many parts of the world causing large-scale outbreaks. CHIKV infection presents as a febrile illness known as chikungunya fever (CHIKF). Infection is self-limited and characterized mainly by severe joint pain and myalgia that can last for weeks or months; however, severe disease presentation can also occur in a minor proportion of infections. Among the atypical CHIKV manifestations that have been described, severe arthralgia and neurological complications, such as encephalitis, meningitis, and Guillain–Barré Syndrome, are now reported in many outbreaks. Moreover, death cases were also reported, placing CHIKV as a relevant public health disease. Virus evolution, globalization, and climate change may have contributed to CHIKV spread. In addition to this, the lack of preventive vaccines and approved antiviral treatments is turning CHIKV into a major global health threat. In this review, we discuss the current knowledge about CHIKV pathogenesis, with a focus on atypical disease manifestations, such as persistent arthralgia and neurologic disease presentation. We also bring an up-to-date review of the current CHIKV vaccine development. Altogether, these topics highlight some of the most recent advances in our understanding of CHIKV pathogenesis and also provide important insights into the current development and clinical trials of CHIKV potential vaccine candidates. Full article

(This article belongs to the Special Issue Chikungunya Virus and Emerging Alphaviruses)

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Open AccessSystematic Review

Heart Disease and Arboviruses: A Systematic Review and Meta-Analysis

Jandir Mendonça Nicacio

Orlando Vieira Gomes

Rodrigo Feliciano do Carmo

Sávio Luiz Pereira Nunes

José Roberto Coelho Ferreira Rocha

Carlos Dornels Freire de Souza

Rafael Freitas de Oliveira Franca

Ricardo Khouri

Manoel Barral-Netto

and

Anderson da Costa Armstrong

Viruses 2022, 14(9), 1988; https://doi.org/10.3390/v14091988 - 08 Sep 2022

Cited by 2 | Viewed by 1702

Abstract

Dengue fever, chikungunya, and zika are highly prevalent arboviruses transmitted by hematophagous arthropods, with a widely neglected impact in developing countries. These diseases cause acute illness in diverse populations, as well as potential cardiovascular complications. A systematic review was carried out to investigate the burden of cardiac involvement related to these arboviruses. Multiple databases were searched for articles that investigated the association of cardiovascular diseases with arboviruses, published up to March 2022. Relevant articles were selected and rated by two independent reviewers. Proportion meta-analysis was applied to assess the frequency-weighted mean of the cardiovascular findings. A total of 42 articles were selected (n = 76,678 individuals), with 17 manuscripts on dengue and 6 manuscripts on chikungunya undergoing meta-analysis. The global pooled incidence of cardiac events in dengue fever using a meta-analysis was 27.21% (95% CI 20.21–34.83; I² = 94%). The higher incidence of dengue-related myocarditis was found in the population younger than 20 years old (33.85%; 95% CI 0.00–89.20; I² = 99%). Considering the studies on chikungunya (n = 372), the global pooled incidence of cardiac involvement using a meta-analysis was 32.81% (95% CI 09.58–61.49, I² = 96%). Two Zika studies were included that examined cases of infection by vertical transmission in Brazil, finding everything from structural changes to changes in heart rate variability that increase the risk of sudden death. In conclusion, cardiac involvement in arboviruses is not uncommon, especially in dengue fever. Full article

(This article belongs to the Special Issue Chikungunya Virus and Emerging Alphaviruses)

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