Chikungunya Virus and (Re-) Emerging Alphaviruses

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

Deadline for manuscript submissions: closed (28 February 2019) | Viewed by 97895

Special Issue Editors


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Guest Editor
Department of Immunology, School of Medicine, the University of Connecticut Health Center, Farmington, CT, USA
Interests: immunology; infectious disease; Arbovirus; innate immunity
Special Issues, Collections and Topics in MDPI journals
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
Interests: arboviruses; alphaviruses; flaviruses; genetic screens; virus–host interactions

Special Issue Information

Dear Colleagues,

Since 2003, the “Old World” chikungunya virus has re-emerged and spread throughout the world in more than 40 countries, posing a big threat to public health. This mosquito-borne virus, belonging to the genus of Alphavirus in the family of Togaviridae, causes acute infection with symptoms ranging from fever, rash, myalgia, to severe arthralgia and arthritis. Although with a low fatality rate, this virus can produce chronic infection, characterized by muscle and joint pain which afflicts patients for months to years and has a substantial impact on their quality of life. Additionally, the (re-) emergence of other members of the genus Alphavirus that cause severe diseases in animals and/or humans has raised great concerns. Therefore, an overview of alphavirus research is timely and will greatly help the control and prevention of viral disease transmission.

In this Special Issue, we welcome the alphavirus community to submit research articles or review papers related to all aspects of chikungunya virus and other (re-) emerging alphaviruses, from virus discovery, phylogenetic and epidemiological studies, clinical diagnostics to basic research including, but not limited to, virus entry, cross-species transmission, replication and gene expression, viral immunity, and pathogenesis. Studies on the development of novel detection strategies, neutralizing antibodies, vaccines, and antiviral therapeutics are welcome.

Dr. Penghua Wang
Dr. Rong Zhang
Guest Editors

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Keywords

  • chikungunya virus
  • alphavirus
  • virus entry
  • viral immunity
  • pathogenesis
  • replication and gene expression
  • epidemiology
  • vaccine
  • neutralizing antibody
  • therapeutics

Published Papers (17 papers)

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Editorial

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3 pages, 173 KiB  
Editorial
Chikungunya Virus and (Re-) Emerging Alphaviruses
by Penghua Wang and Rong Zhang
Viruses 2019, 11(9), 779; https://0-doi-org.brum.beds.ac.uk/10.3390/v11090779 - 24 Aug 2019
Cited by 3 | Viewed by 3420
Abstract
Alphaviruses belong to a family of positive sense, single-stranded RNA viruses that are transmitted mainly by mosquitoes through a blood meal and cause arthritis and/or encephalitis in humans and animals [...] Full article
(This article belongs to the Special Issue Chikungunya Virus and (Re-) Emerging Alphaviruses)

Research

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16 pages, 9470 KiB  
Article
Genetic Variability of Chikungunya Virus in Southern Mexico
by Kame A. Galan-Huerta, Viviana C. Zomosa-Signoret, Román Vidaltamayo, Sandra Caballero-Sosa, Ildefonso Fernández-Salas, Javier Ramos-Jiménez and Ana M. Rivas-Estilla
Viruses 2019, 11(8), 714; https://0-doi-org.brum.beds.ac.uk/10.3390/v11080714 - 05 Aug 2019
Cited by 3 | Viewed by 3475
Abstract
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes Chikungunya fever. CHIKV entered Mexico through the state of Chiapas in October 2014. To fully understand the Chikungunya fever outbreak that occurred in southern Chiapas during 2015, we evaluated 22 PCR-confirmed CHIKV-positive patients, identified [...] Read more.
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes Chikungunya fever. CHIKV entered Mexico through the state of Chiapas in October 2014. To fully understand the Chikungunya fever outbreak that occurred in southern Chiapas during 2015, we evaluated 22 PCR-confirmed CHIKV-positive patients, identified CHIKV genetic variability, reconstructed viral dispersal, and assessed possible viral mutations. Viruses were isolated and E2, 6K, and E1 genes were sequenced. We applied phylogenetic and phylogeographic approaches, modeled mutations, and estimated selective pressure. Different CHIKV strains circulated in Chiapas during summer 2015. Three isolates grouped themselves in a well-supported clade. Estimates show that the outbreak started in Ciudad Hidalgo and posteriorly dispersed towards Tapachula and neighboring municipalities. We found six non-synonymous mutations in our isolates. Two mutations occurred in one isolate and the remaining mutations occurred in single isolates. Mutations E2 T116I and E2 K221R changed the protein surface in contact with the host cell receptors. We could not find positive selected sites in our CHIKV sequences from southern Chiapas. This is the first viral phylogeographic reconstruction in Mexico characterizing the CHIKV outbreak in southern Chiapas. Full article
(This article belongs to the Special Issue Chikungunya Virus and (Re-) Emerging Alphaviruses)
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17 pages, 3100 KiB  
Article
Bioluminescent Ross River Virus Allows Live Monitoring of Acute and Long-Term Alphaviral Infection by In Vivo Imaging
by Essia Belarbi, Vincent Legros, Justine Basset, Philippe Desprès, Pierre Roques and Valérie Choumet
Viruses 2019, 11(7), 584; https://doi.org/10.3390/v11070584 - 27 Jun 2019
Cited by 11 | Viewed by 3768
Abstract
Arboviruses like chikungunya and Ross River (RRV) are responsible for massive outbreaks of viral polyarthritis. There is no effective treatment or vaccine available against these viruses that induce prolonged and disabling arthritis. To explore the physiopathological mechanisms of alphaviral arthritis, we engineered a [...] Read more.
Arboviruses like chikungunya and Ross River (RRV) are responsible for massive outbreaks of viral polyarthritis. There is no effective treatment or vaccine available against these viruses that induce prolonged and disabling arthritis. To explore the physiopathological mechanisms of alphaviral arthritis, we engineered a recombinant RRV expressing a NanoLuc reporter (RRV-NLuc), which exhibited high stability, near native replication kinetics and allowed real time monitoring of viral spread in an albino mouse strain. During the acute phase of the disease, we observed a high bioluminescent signal reflecting viral replication and dissemination in the infected mice. Using Bindarit, an anti-inflammatory drug that inhibits monocyte recruitment, we observed a reduction in viral dissemination demonstrating the important role of monocytes in the propagation of the virus and the adaptation of this model to the in vivo evaluation of treatment strategies. After resolution of the acute symptoms, we observed an increase in the bioluminescent signal in mice subjected to an immunosuppressive treatment 30 days post infection, thus showing active in vivo replication of remnant virus. We show here that this novel reporter virus is suitable to study the alphaviral disease up to the chronic phase, opening new perspectives for the evaluation of therapeutic interventions. Full article
(This article belongs to the Special Issue Chikungunya Virus and (Re-) Emerging Alphaviruses)
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22 pages, 3474 KiB  
Article
Establishment and Comparison of Pathogenicity and Related Neurotropism in Two Age Groups of Immune Competent Mice, C57BL/6J Using an Indian Isolate of Chikungunya Virus (CHIKV)
by Jaspreet Jain, Vimal Narayanan, Ankit Kumar, Jatin Shrinet, Priyanshu Srivastava, Shivam Chaturvedi and Sujatha Sunil
Viruses 2019, 11(6), 578; https://0-doi-org.brum.beds.ac.uk/10.3390/v11060578 - 25 Jun 2019
Cited by 6 | Viewed by 3709
Abstract
Chikungunya (CHIK) is a febrile arboviral illness caused by chikungunya virus (CHIKV) and has been identified in more than 60 countries across the globe. A major public health concern, the infection occurs as an acute febrile phase and a chronic arthralgic phase. The [...] Read more.
Chikungunya (CHIK) is a febrile arboviral illness caused by chikungunya virus (CHIKV) and has been identified in more than 60 countries across the globe. A major public health concern, the infection occurs as an acute febrile phase and a chronic arthralgic phase. The disease manifests differently in different age groups that can range from asymptomatic infection in the younger age group to a prolonged chronic phase in the elderly population. The present study was undertaken to evaluate strain-specific pathogenesis of ECSA genotype of CHIKV strains derived from clinical isolates in adult C57BL/6J mice model. The strain that was pathogenic and developed distinct acute and post–acute phase of CHIK infection was further evaluated for dose-dependent pathogenesis. Upon arriving on the optimal dose to induce clinical symptoms in the mice, the disease progression was evaluated across the acute and the post–acute phase of infection for a period of 15 days post–infection in two age groups of mice, namely eight weeks old and 20 weeks old mice groups. Biochemical, hematological, and virology attributes were measured and correlated to morbidity and linked neurotropism and limb thickness in the two age groups. Our results show that CHIKV exhibit strain-specific pathogenesis in C57BL/6J mice. Distinct dissimilarities were observed between the two age groups in terms of pathogenesis, viral clearance and host response to CHIKV infection. Full article
(This article belongs to the Special Issue Chikungunya Virus and (Re-) Emerging Alphaviruses)
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12 pages, 871 KiB  
Communication
RNASeq Analysis of Aedes albopictus Mosquito Midguts after Chikungunya Virus Infection
by Ravi kiran Vedururu, Matthew J. Neave, Mary Tachedjian, Melissa J. Klein, Paul R. Gorry, Jean-Bernard Duchemin and Prasad N. Paradkar
Viruses 2019, 11(6), 513; https://0-doi-org.brum.beds.ac.uk/10.3390/v11060513 - 04 Jun 2019
Cited by 17 | Viewed by 4597
Abstract
Chikungunya virus (CHIKV) is an emerging pathogen around the world and causes significant morbidity in patients. A single amino acid mutation in the envelope protein of CHIKV has led to a shift in vector preference towards Aedes albopictus. While mosquitoes are known [...] Read more.
Chikungunya virus (CHIKV) is an emerging pathogen around the world and causes significant morbidity in patients. A single amino acid mutation in the envelope protein of CHIKV has led to a shift in vector preference towards Aedes albopictus. While mosquitoes are known to mount an antiviral immune response post-infection, molecular interactions during the course of infection at the tissue level remain largely uncharacterised. We performed whole transcriptome analysis on dissected midguts of Aedes albopictus infected with CHIKV to identify differentially expressed genes. For this, RNA was extracted at two days post-infection (2-dpi) from pooled midguts. We initially identified 25 differentially expressed genes (p-value < 0.05) when mapped to a reference transcriptome. Further, multiple differentially expressed genes were identified from a custom de novo transcriptome, which was assembled using the reads that did not align with the reference genome. Thirteen of the identified transcripts, possibly involved in immunity, were validated by qRT-PCR. Homologues of seven of these genes were also found to be significantly upregulated in Aedes aegypti midguts 2 dpi, indicating a conserved mechanism at play. These results will help us to characterise the molecular interaction between Aedes albopictus and CHIKV and can be utilised to reduce the impact of this viral infection. Full article
(This article belongs to the Special Issue Chikungunya Virus and (Re-) Emerging Alphaviruses)
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13 pages, 2731 KiB  
Article
Development of an E2 ELISA Methodology to Assess Chikungunya Seroprevalence in Patients from an Endemic Region of Mexico
by Young Chan Kim, César López-Camacho, Nallely Garcia-Larragoiti, Alan Cano-Mendez, Karina Guadalupe Hernandez-Flores, Carlos Alonso Domínguez-Alemán, Maria Antonieta Mar, Héctor Vivanco-Cid, Martha Eva Viveros-Sandoval and Arturo Reyes-Sandoval
Viruses 2019, 11(5), 407; https://0-doi-org.brum.beds.ac.uk/10.3390/v11050407 - 01 May 2019
Cited by 8 | Viewed by 5139
Abstract
Chikungunya fever is a debilitating disease caused by Chikungunya virus (CHIKV) that can result in long-lasting arthralgias. The early diagnosis of CHIKV relies on PCR during the acute infection phase to allow differential diagnosis with other co-circulating arboviruses such as dengue and Zika. [...] Read more.
Chikungunya fever is a debilitating disease caused by Chikungunya virus (CHIKV) that can result in long-lasting arthralgias. The early diagnosis of CHIKV relies on PCR during the acute infection phase to allow differential diagnosis with other co-circulating arboviruses such as dengue and Zika. Alternatively, serology can support diagnosis and provide epidemiological information on current and past outbreaks. Many commercial serological ELISA assays are based on the inactivated whole CHIKV, but their sensitivity and specificity show great variability. We produced recombinant CHIKV E2 that is suitable for ELISA assays, which was used for the serodiagnosis of CHIKV infections occurring in an arbovirus endemic Mexican region within Michoacán state. A cross-sectional study was conducted in 2016–2017; sera was obtained from 15 healthy donors and 68 patients presenting undifferentiated febrile illness. Serum samples were screened by RT-PCR and by our in-house ELISA assay. Our results indicate that IgM and IgG anti-CHIKV E2 antibodies were detected with our ELISA assay with higher sensitivity than a commercially available CHIKV ELISA kit. Our simple and sensitive ELISA assay for the serodiagnosis of CHIKV infections can be applied to population-based seroprevalence surveys and has potential for monitoring vaccine immunogenicity in CHIKV vaccine clinical trials. Full article
(This article belongs to the Special Issue Chikungunya Virus and (Re-) Emerging Alphaviruses)
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12 pages, 1036 KiB  
Article
Experimental Vertical Transmission of Chikungunya Virus by Brazilian and Florida Aedes Albopictus Populations
by Nildimar Alves Honório, Keenan Wiggins, Bradley Eastmond, Daniel Cardoso Portela Câmara and Barry W. Alto
Viruses 2019, 11(4), 353; https://0-doi-org.brum.beds.ac.uk/10.3390/v11040353 - 17 Apr 2019
Cited by 22 | Viewed by 5316
Abstract
Chikungunya virus (CHIKV) is a vector-borne alphavirus transmitted by the bites of mosquitoes, specifically infected, female mosquitoes of the invasive Aedes species. In nature, CHIKV can be maintained by vertical transmission, a phenomenon that relates to the transfer of CHIKV from the infected [...] Read more.
Chikungunya virus (CHIKV) is a vector-borne alphavirus transmitted by the bites of mosquitoes, specifically infected, female mosquitoes of the invasive Aedes species. In nature, CHIKV can be maintained by vertical transmission, a phenomenon that relates to the transfer of CHIKV from the infected parent to their offspring within the ovary or during oviposition. In the present study, we conducted laboratory experiments to determine vertical transmission with Ae. albopictus populations from Brazil and Florida. Parental Ae. albopictus females were orally infected with the emergent Asian genotype of CHIKV in the first gonotrophic cycle (infectious blood meal) and tested for vertical transmission following the second (non-infectious blood meal) gonotrophic cycle. CHIKV infection and CHIKV viral titer in parental females were significantly related to population origin, with Brazilian Ae. albopictus showing higher viral dissemination and viral titer than the Florida population. Experimental vertical transmission of CHIKV was documented in one pool of female and four pools of male Ae. albopictus from Brazil (minimum infection rate, MIR, of 0.76% and 2.86%, respectively, for females and males). For the Florida population of Ae. albopictus, only one pool of males was positive for CHIKV infection, with an MIR of 1.06%. Our results demonstrate that Ae. albopictus populations from Brazil and Florida show heterogeneous CHIKV dissemination and vertical transmission, which may contribute to the epidemiology of CHIKV and may be particularly relevant to virus survival during inter-epidemic periods. Full article
(This article belongs to the Special Issue Chikungunya Virus and (Re-) Emerging Alphaviruses)
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17 pages, 11006 KiB  
Article
Assessment of Immunogenicity and Neutralisation Efficacy of Viral-Vectored Vaccines Against Chikungunya Virus
by César López-Camacho, Young Chan Kim, Joshua Blight, Marcos Lazaro Moreli, Eduardo Montoya-Diaz, Juha T Huiskonen, Beate Mareike Kümmerer and Arturo Reyes-Sandoval
Viruses 2019, 11(4), 322; https://0-doi-org.brum.beds.ac.uk/10.3390/v11040322 - 03 Apr 2019
Cited by 31 | Viewed by 8126
Abstract
Chikungunya virus (CHIKV) has caused extensive outbreaks in several countries within the Americas, Asia, Oceanic/Pacific Islands, and Europe. In humans, CHIKV infections cause a debilitating disease with acute febrile illness and long-term polyarthralgia. Acute and chronic symptoms impose a major economic burden to [...] Read more.
Chikungunya virus (CHIKV) has caused extensive outbreaks in several countries within the Americas, Asia, Oceanic/Pacific Islands, and Europe. In humans, CHIKV infections cause a debilitating disease with acute febrile illness and long-term polyarthralgia. Acute and chronic symptoms impose a major economic burden to health systems and contribute to poverty in affected countries. An efficacious vaccine would be an important step towards decreasing the disease burden caused by CHIKV infection. Despite no licensed vaccine is yet available for CHIKV, there is strong evidence of effective asymptomatic viral clearance due to neutralising antibodies against the viral structural proteins. We have designed viral-vectored vaccines to express the structural proteins of CHIKV, using the replication-deficient chimpanzee adenoviral platform, ChAdOx1. Expression of the CHIKV antigens results in the formation of chikungunya virus-like particles. Our vaccines induce high frequencies of anti-chikungunya specific T-cell responses as well as high titres of anti-CHIKV E2 antibodies with high capacity for in vitro neutralisation. Our results indicate the potential for further clinical development of the ChAdOx1 vaccine platform in CHIKV vaccinology. Full article
(This article belongs to the Special Issue Chikungunya Virus and (Re-) Emerging Alphaviruses)
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13 pages, 1409 KiB  
Article
Inactivation and Removal of Chikungunya Virus and Mayaro Virus from Plasma-derived Medicinal Products
by Constanze Yue, Sebastian Teitz, Tomoyuki Miyabashi, Klaus Boller, Lia Laura Lewis-Ximenez, Sally A. Baylis and Johannes Blümel
Viruses 2019, 11(3), 234; https://0-doi-org.brum.beds.ac.uk/10.3390/v11030234 - 07 Mar 2019
Cited by 11 | Viewed by 4835
Abstract
Background: Chikungunya virus (CHIKV) and Mayaro virus (MAYV) are closely related members of the Semliki Forest complex within the genus alphavirus and are transmitted by arthropods, causing acute febrile illness in humans. CHIKV has spread to almost all continents, whereas autochthonous MAYV infections [...] Read more.
Background: Chikungunya virus (CHIKV) and Mayaro virus (MAYV) are closely related members of the Semliki Forest complex within the genus alphavirus and are transmitted by arthropods, causing acute febrile illness in humans. CHIKV has spread to almost all continents, whereas autochthonous MAYV infections have been reported in South America and in the Caribbean. Nevertheless, there was concern about potential spread of MAYV to other regions similar to CHIKV in the past. The risk for transmission of emerging viruses by blood transfusion and the safety of plasma-derived medicinal products (PDMPs) are constant concerns. The manufacturing processes of PDMPs include procedures to inactivate/remove viruses. Methods: In this study, we investigated the reduction of MAYV and CHIKV by heat inactivation in various matrices, solvent/detergent treatment and nanofiltration. Results: Unexpectedly, MAYV was significantly more resistant to heat and solvent/detergent treatment compared to CHIKV. However, being similar in size, both MAYV and CHIKV were removed below the detection limit by 35 nm virus filters. Conclusions: The inactivation profiles of different alphavirus members vary considerably, even within the Semliki Forest Complex. However, robust dedicated viral inactivation/removal procedures commonly used in the plasma product industry are effective in inactivating or removing MAYV and CHIKV. Full article
(This article belongs to the Special Issue Chikungunya Virus and (Re-) Emerging Alphaviruses)
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11 pages, 1606 KiB  
Article
Silvestrol Inhibits Chikungunya Virus Replication
by Lisa Henss, Tatjana Scholz, Arnold Grünweller and Barbara S. Schnierle
Viruses 2018, 10(11), 592; https://0-doi-org.brum.beds.ac.uk/10.3390/v10110592 - 30 Oct 2018
Cited by 34 | Viewed by 4492
Abstract
Silvestrol, a natural compound that is isolated from plants of the genus Aglaia, is a specific inhibitor of the RNA helicase eIF4A, which unwinds RNA secondary structures in 5′-untranslated regions (UTRs) of mRNAs and allows translation. Silvestrol has a broad antiviral activity [...] Read more.
Silvestrol, a natural compound that is isolated from plants of the genus Aglaia, is a specific inhibitor of the RNA helicase eIF4A, which unwinds RNA secondary structures in 5′-untranslated regions (UTRs) of mRNAs and allows translation. Silvestrol has a broad antiviral activity against multiple RNA virus families. Here, we show that silvestrol inhibits the replication of chikungunya virus (CHIKV), a positive single-stranded RNA virus. Silvestrol delayed the protein synthesis of non-structural (nsPs) and structural proteins, resulting in a delayed innate response to CHIKV infection. Interferon-α induced STAT1 phosphorylation was not inhibited nor did eIF2α become phosphorylated 16 h post infection in the presence of silvestrol. In addition, the host protein shut-off induced by CHIKV infection was decreased in silvestrol-treated cells. Silvestrol acts by limiting the amount of nsPs, and thereby reducing CHIKV RNA replication. From our results, we propose that inhibition of the host helicase eIF4A might have potential as a therapeutic strategy to treat CHIKV infections. Full article
(This article belongs to the Special Issue Chikungunya Virus and (Re-) Emerging Alphaviruses)
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20 pages, 5235 KiB  
Article
Ultrastructural Analysis of Chikungunya Virus Dissemination from the Midgut of the Yellow Fever Mosquito, Aedes aegypti
by Asher M. Kantor, DeAna G. Grant, Velmurugan Balaraman, Tommi A. White and Alexander W. E. Franz
Viruses 2018, 10(10), 571; https://0-doi-org.brum.beds.ac.uk/10.3390/v10100571 - 18 Oct 2018
Cited by 30 | Viewed by 7214
Abstract
The transmission cycle of chikungunya virus (CHIKV) requires that mosquito vectors get persistently infected with the virus, following its oral acqsuisition from a vertebrate host. The mosquito midgut is the initial organ that gets infected with orally acquired CHIKV. Following its replication in [...] Read more.
The transmission cycle of chikungunya virus (CHIKV) requires that mosquito vectors get persistently infected with the virus, following its oral acqsuisition from a vertebrate host. The mosquito midgut is the initial organ that gets infected with orally acquired CHIKV. Following its replication in the midgut epithelium, the virus exits the midgut and infects secondary tissues including the salivary glands before being transmitted to another host. Here, we investigate the pattern of CHIKV dissemination from the midgut of Aedes aegypti at the ultrastructural level. Bloodmeal ingestion caused overstretching of the midgut basal lamina (BL), which was disrupted in areas adjacent to muscles surrounding the midgut as shown by scanning electron microscopy (SEM). Using both transmission electron microscopy (TEM) and focused ion beam scanning electron microscopy (FIB-SEM) to analyze midgut preparations, mature chikungunya (CHIK) virions were found accumulating at the BL and within strands of the BL at 24–32 h post-infectious bloodmeal (pibm). From 48 h pibm onwards, virions no longer congregated at the BL and became dispersed throughout the basal labyrinth of the epithelial cells. Ingestion of a subsequent, non-infectious bloodmeal caused mature virions to congregate again at the midgut BL. Our study suggests that CHIKV needs a single replication cycle in the midgut epithelium before mature virions directly traverse the midgut BL during a relatively narrow time window, within 48 h pibm. Full article
(This article belongs to the Special Issue Chikungunya Virus and (Re-) Emerging Alphaviruses)
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Review

Jump to: Editorial, Research

8 pages, 1947 KiB  
Review
Chikungunya Virus Infections in Military Deployments in Tropical Settings—A Narrative Minireview
by Hagen Frickmann and Ottmar Herchenröder
Viruses 2019, 11(6), 550; https://0-doi-org.brum.beds.ac.uk/10.3390/v11060550 - 14 Jun 2019
Cited by 6 | Viewed by 4926
Abstract
Chikungunya fever is a vector-borne viral disease in subtropical and tropical areas of endemicity. Apart from the burden on local populations, chikungunya virus infection also poses a risk for travelers and, in particular, soldiers during prolonged deployment-associated outdoor activities. The absence of rapid [...] Read more.
Chikungunya fever is a vector-borne viral disease in subtropical and tropical areas of endemicity. Apart from the burden on local populations, chikungunya virus infection also poses a risk for travelers and, in particular, soldiers during prolonged deployment-associated outdoor activities. The absence of rapid diagnostic tests makes surveillance challenging during military deployments in war and crisis zones with restricted medical infrastructure. Consequently, both historical and up-to-date surveillance data from battlefields are scarce. From several studies and postdeployment assessments, some information on the epidemiology of chikungunya virus infections in deployed military personnel is nevertheless available. The few published data homogeneously suggest a low infection risk in the endemic setting. During outbreaks, however, the infection risk of military personnel is comparable to that of the local population. Infection clusters of soldiers without pronounced outdoor activity have been reported under such circumstances as well. In spite of efforts focusing on the development of a chikungunya virus vaccine, no licensed product is available so far. Full article
(This article belongs to the Special Issue Chikungunya Virus and (Re-) Emerging Alphaviruses)
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17 pages, 2973 KiB  
Review
Antiviral Functions of Monoclonal Antibodies against Chikungunya Virus
by Jing Jin and Graham Simmons
Viruses 2019, 11(4), 305; https://0-doi-org.brum.beds.ac.uk/10.3390/v11040305 - 28 Mar 2019
Cited by 32 | Viewed by 8769
Abstract
Chikungunya virus (CHIKV) is the most common alphavirus infecting humans worldwide. Antibodies play pivotal roles in the immune response to infection. Increasingly, therapeutic antibodies are becoming important for protection from pathogen infection for which neither vaccine nor treatment is available, such as CHIKV [...] Read more.
Chikungunya virus (CHIKV) is the most common alphavirus infecting humans worldwide. Antibodies play pivotal roles in the immune response to infection. Increasingly, therapeutic antibodies are becoming important for protection from pathogen infection for which neither vaccine nor treatment is available, such as CHIKV infection. The new generation of ultra-potent and/or broadly cross-reactive monoclonal antibodies (mAbs) provides new opportunities for intervention. In the past decade, several potent human and mouse anti-CHIKV mAbs were isolated and demonstrated to be protective in vivo. Mechanistic studies of these mAbs suggest that mAbs exert multiple modes of action cooperatively. Better understanding of these antiviral mechanisms for mAbs will help to optimize mAb therapies. Full article
(This article belongs to the Special Issue Chikungunya Virus and (Re-) Emerging Alphaviruses)
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20 pages, 557 KiB  
Review
Chikungunya in Infants and Children: Is Pathogenesis Increasing?
by Kelli L. Barr and Vedana Vaidhyanathan
Viruses 2019, 11(3), 294; https://0-doi-org.brum.beds.ac.uk/10.3390/v11030294 - 23 Mar 2019
Cited by 28 | Viewed by 5087
Abstract
Chikungunya virus (CHIKV) was first extensively described in children during outbreaks in India and South Asia during the mid-1960s. Prior to the 2005 emergence of CHIKV on Reunion Island, CHIKV infection was usually described as a dengue-like illness with arthralgia in Africa and [...] Read more.
Chikungunya virus (CHIKV) was first extensively described in children during outbreaks in India and South Asia during the mid-1960s. Prior to the 2005 emergence of CHIKV on Reunion Island, CHIKV infection was usually described as a dengue-like illness with arthralgia in Africa and febrile hemorrhagic disease in Asia. Soon after the 2005 emergence, severe CNS consequences from vertical and perinatal transmission were described and as CHIKV continued to emerge in new areas over the next 10 years, severe manifestation of infection and sequelae were increasingly reported in infants and neonates. The following review describes the global reemergence and the syndromes of Chikungunya fever (CHIKF) in infants and children. The various manifestations of CHIKF are described and connected to the viral lineage that was documented in the area at the time the disease was described. The data show that certain manifestations of CHIKF occur with specific viral lineages and genetic motifs, which suggests that severe manifestations of CHIKF in the very young may be associated with the emergence of new viral lineages. Full article
(This article belongs to the Special Issue Chikungunya Virus and (Re-) Emerging Alphaviruses)
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12 pages, 1625 KiB  
Review
The Clinical Features, Pathogenesis and Methotrexate Therapy of Chronic Chikungunya Arthritis
by J. Kennedy Amaral, Peter C. Taylor, Mauro Martins Teixeira, Thomas E. “Tem” Morrison and Robert T. Schoen
Viruses 2019, 11(3), 289; https://0-doi-org.brum.beds.ac.uk/10.3390/v11030289 - 22 Mar 2019
Cited by 22 | Viewed by 6310
Abstract
Chikungunya fever (CHIKF) is an emerging viral infection that has spread widely, along with its Aedes vectors, throughout the tropics and beyond, causing explosive epidemics of acute illness and persistent disabling arthritis. The rheumatic symptoms associated with chikungunya virus (CHIKV) infection include polyarthralgia, [...] Read more.
Chikungunya fever (CHIKF) is an emerging viral infection that has spread widely, along with its Aedes vectors, throughout the tropics and beyond, causing explosive epidemics of acute illness and persistent disabling arthritis. The rheumatic symptoms associated with chikungunya virus (CHIKV) infection include polyarthralgia, polyarthritis, morning stiffness, joint edema, and erythema. Chronic CHIK arthritis (CCA) often causes severe pain and associated disability. The pathogenesis of CCA is not well understood. Proposed hypotheses include the persistence of a low level of replicating virus in the joints, the persistence of viral RNA in the synovium, and the induction of autoimmunity. In this review, we describe the main hypotheses of CCA pathogenesis, some of which support methotrexate (MTX) treatment which has been shown to be effective in preliminary studies in CCA. Full article
(This article belongs to the Special Issue Chikungunya Virus and (Re-) Emerging Alphaviruses)
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26 pages, 945 KiB  
Review
Tropism of the Chikungunya Virus
by Giulia Matusali, Francesca Colavita, Licia Bordi, Eleonora Lalle, Giuseppe Ippolito, Maria R. Capobianchi and Concetta Castilletti
Viruses 2019, 11(2), 175; https://0-doi-org.brum.beds.ac.uk/10.3390/v11020175 - 20 Feb 2019
Cited by 78 | Viewed by 10573
Abstract
Chikungunya virus (CHIKV) is a re-emerging mosquito-borne virus that displays a large cell and organ tropism, and causes a broad range of clinical symptoms in humans. It is maintained in nature through both urban and sylvatic cycles, involving mosquito vectors and human or [...] Read more.
Chikungunya virus (CHIKV) is a re-emerging mosquito-borne virus that displays a large cell and organ tropism, and causes a broad range of clinical symptoms in humans. It is maintained in nature through both urban and sylvatic cycles, involving mosquito vectors and human or vertebrate animal hosts. Although CHIKV was first isolated in 1953, its pathogenesis was only more extensively studied after its re-emergence in 2004. The unexpected spread of CHIKV to novel tropical and non-tropical areas, in some instances driven by newly competent vectors, evidenced the vulnerability of new territories to this infectious agent and its associated diseases. The comprehension of the exact CHIKV target cells and organs, mechanisms of pathogenesis, and spectrum of both competitive vectors and animal hosts is pivotal for the design of effective therapeutic strategies, vector control measures, and eradication actions. Full article
(This article belongs to the Special Issue Chikungunya Virus and (Re-) Emerging Alphaviruses)
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14 pages, 409 KiB  
Review
Genetic Determinants of the Re-Emergence of Arboviral Diseases
by Harshada Ketkar, Daniella Herman and Penghua Wang
Viruses 2019, 11(2), 150; https://0-doi-org.brum.beds.ac.uk/10.3390/v11020150 - 12 Feb 2019
Cited by 23 | Viewed by 6773
Abstract
Mosquito-borne diseases constitute a large portion of infectious diseases, causing more than 700,000 deaths annually. Mosquito-transmitted viruses, such as yellow fever, dengue, West Nile, chikungunya, and Zika viruses, have re-emerged recently and remain a public health threat worldwide. Global climate change, rapid urbanization, [...] Read more.
Mosquito-borne diseases constitute a large portion of infectious diseases, causing more than 700,000 deaths annually. Mosquito-transmitted viruses, such as yellow fever, dengue, West Nile, chikungunya, and Zika viruses, have re-emerged recently and remain a public health threat worldwide. Global climate change, rapid urbanization, burgeoning international travel, expansion of mosquito populations, vector competence, and host and viral genetics may all together contribute to the re-emergence of arboviruses. In this brief review, we summarize the host and viral genetic determinants that may enhance infectivity in the host, viral fitness in mosquitoes and viral transmission by mosquitoes. Full article
(This article belongs to the Special Issue Chikungunya Virus and (Re-) Emerging Alphaviruses)
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