Infectious #cDNA #clones of two #strains of #Mayaro virus for studies on viral #pathogenesis and #vaccine development (Virology, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Virology. 2019 Jul 14;535:227-231. doi: 10.1016/j.virol.2019.07.013. [Epub ahead of print]

Infectious cDNA clones of two strains of Mayaro virus for studies on viral pathogenesis and vaccine development.

Chuong C1, Bates TA1, Weger-Lucarelli J2.

Author information: 1 Department of Biomedical Sciences and Pathobiology, Virginia Tech, VA-MD Regional College of Veterinary Medicine, Blacksburg, VA, USA. 2 Department of Biomedical Sciences and Pathobiology, Virginia Tech, VA-MD Regional College of Veterinary Medicine, Blacksburg, VA, USA. Electronic address: weger@vt.edu.

 

Abstract

Mayaro virus (MAYV; family Togaviridae, genus Alphavirus) is an emerging global threat that can cause severe clinical manifestations similar to Zika, dengue, and chikungunya viruses. Currently, there is a lack of molecular tools to enable a better understanding of the transmission and pathogenesis of MAYV. Here, we detail the development and characterization of infectious clones of two strains of MAYV that produce infectious virus and replicate in mammalian and mosquito cells similarly to wild-type virus. Additionally, clone-derived viruses produced identical infection rates and phenotypes in CD-1 mice compared to the parental strains. This infectious clone system will provide a resource to the research community to analyze MAYV genetic determinants of virulence, determine vector competence, and develop vaccines.

Copyright © 2019 Elsevier Inc. All rights reserved.

KEYWORDS: Alphavirus; Infectious clones; Mayaro virus

PMID: 31325837 DOI: 10.1016/j.virol.2019.07.013

Keywords: Alphavirus; Togavirus; Mayaro virus; Viral pathogenesis.

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#Chikungunya virus #vaccine candidates with decreased mutational robustness are attenuated in vivo and have compromised transmissibility (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

Chikungunya virus vaccine candidates with decreased mutational robustness are attenuated in vivo and have compromised transmissibility.

Lucía Carrau, Veronica V. Rezelj, María G. Noval, Laura I. Levi, Daniela Megrian, Herve Blanc, James Weger-Lucarelli, Gonzalo Moratorio, Kenneth Stapleford, Marco Vignuzzi

DOI: 10.1128/JVI.00775-19

 

ABSTRACT

Chikungunya virus (CHIKV) is a re-emerged arbovirus, member of the Togaviridae family. It circulates through mosquito vectors mainly of the Aedes family and a mammalian host. CHIKV causes chikungunya fever, a mild to severe disease characterized by arthralgia, with some fatal outcomes described. In the past years, several outbreaks mainly caused by enhanced adaptation of the virus to the vector and ineffective control of the contacts between infected mosquito populations and the human host have been reported. Vaccines represent the best solution for the control of insect-borne viruses, including CHIKV, but are often unavailable. We designed live attenuated CHIKV by applying a rational genomic design based on multiple replacements of synonymous codons. In doing so, the virus mutational robustness (capacity to maintain phenotype despite introduction of mutations to genotype) is decreased, driving the viral population towards deleterious evolutionary trajectories. When tested in the insect and mammalian hosts, we observed overall strong attenuation in both and greatly diminished signs of disease. Moreover, we found the vaccine candidates elicited protective immunity, related to the production of neutralizing antibodies after a single dose. During an experimental transmission cycle between mosquitoes and naïve mice, vaccine candidates could be transmitted by mosquito bite leading to asymptomatic infection in mice with compromised dissemination. Using deep sequencing technology we observed an increase in detrimental (stop) codons, which confirmed the effectiveness of this genomic design. Because the approach involves hundreds of synonymous modifications to the genome, the reversion risk is significantly reduced, rendering them promising vaccine candidates.

 

IMPORTANCE

Chikungunya fever is a debilitating disease that causes severe pain to the joints, which can compromise the patient’s lifestyle for several months and even in some grave cases lead to death. The etiological agent is chikungunya virus, an alphavirus transmitted by mosquito bite. Currently there are no approved vaccines or treatments against the disease. In our research, we developed novel live attenuated vaccine candidates against chikungunya virus by applying an innovative genomic design. When tested in the insect and mammalian host, the vaccine candidates did not cause disease, elicited strong protection against further infection and had low risk of reversion to pathogenic phenotypes.

Copyright © 2019 Carrau et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Keywords: Alphavirus; Togavirus; Chikungunya fever; Vaccines.

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#Anopheles #mosquitoes may drive invasion and #transmission of #Mayaro virus across geographically diverse regions (PLoS Negl Trop Dis., abstract)

[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Anopheles mosquitoes may drive invasion and transmission of Mayaro virus across geographically diverse regions

Marco Brustolin , Sujit Pujhari , Cory A. Henderson, Jason L. Rasgon

Published: November 7, 2018 / DOI: https://doi.org/10.1371/journal.pntd.0006895 / This is an uncorrected proof.

 

Abstract

The Togavirus (Alphavirus) Mayaro virus (MAYV) was initially described in 1954 from Mayaro County (Trinidad) and has been responsible for outbreaks in South America and the Caribbean. Imported MAYV cases are on the rise, leading to invasion concerns similar to Chikungunya and Zika viruses. Little is known about the range of mosquito species that are competent MAYV vectors. We tested vector competence of 2 MAYV genotypes in laboratory strains of six mosquito species (Aedes aegypti, Anopheles freeborni, An. gambiae, An. quadrimaculatus, An. stephensi, Culex quinquefasciatus). Ae. aegypti and Cx. quinquefasciatus were poor MAYV vectors, and had either poor or null infection and transmission rates at the tested viral challenge titers. In contrast, all Anopheles species were able to transmit MAYV, and 3 of the 4 species transmitted both genotypes. The Anopheles species tested are divergent and native to widely separated geographic regions (Africa, Asia, North America), suggesting that Anopheles may be important in the invasion and spread of MAYV across diverse regions of the world.

 

Author summary

Mayaro virus (MAYV) is a mosquito-borne Alphavirus responsible for outbreaks in South America and the Caribbean. In this study we infected different species of mosquito (belonging to the genera Aedes, Anopheles and Culex) with MAYV and tested their capacity to transmit the virus at different time points. Results show that Anopheles mosquitoes were competent vectors for 2 genotypes of MAYV, while Aedes and Culex were poor vectors. The capacity of Anopheles mosquitoes to transmit MAYV highlights their importance as neglected vectors of arboviruses. These data suggest that Anopheles mosquitoes have the potential to sustain transmission cycles of neglected pathogens in naïve regions, including the United States.

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Citation: Brustolin M, Pujhari S, Henderson CA, Rasgon JL (2018) Anophelesmosquitoes may drive invasion and transmission of Mayaro virus across geographically diverse regions. PLoS Negl Trop Dis 12(11): e0006895. https://doi.org/10.1371/journal.pntd.0006895

Editor: Rebecca C. Christofferson, Louisiana State University, UNITED STATES

Received: July 3, 2018; Accepted: October 3, 2018; Published: November 7, 2018

Copyright: © 2018 Brustolin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All raw data is provided as Supplementary material and in Table 1

Funding: This research was supported by the National Institutes of Health (nih.gov) grants R01AI116636, R01AI128201, and R21AI128918. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Alphavirus; Togavirus; Mayaro Virus; Mosquitoes; Anopheles spp.

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The 2016-2017 #Chikungunya #Outbreak in #Karachi (PLoS Curr., abstract)

[Source: PLoS Currents Outbreaks, full page: (LINK). Abstract, edited.]

The 2016-2017 Chikungunya Outbreak in Karachi

AUGUST 7, 2018 · RESEARCH ARTICLE

REVISIONS: This article is either a revised version or has previous revisions  Edition 1 – August 7, 2018

AUTHORS: Darakhshan Guhar, Shoukat Jahan Talpur, Nadia Jamil, Gulzar Ahmed Channa, Maliha Wajeeh, Muhammad Zohaib Khan, Saifullah Khan

 

ABSTRACT

Introduction:

Chikungunya is an incipient disease, caused by Chikungunya virus (CHKV) that belongs to genus alphavirus of the family Togaviridae.

Materials and Methods:

In this study, during an outbreak of CHKV in Dec 2016 in Karachi, Pakistan, samples were collected from patients presenting with fever, tiredness and pain in muscles and joints. Total 126 sera were tested for the presence of Chikungunya infection through ELISA and Real-time Reverse Transcriptase PCR assay.

Results and Discussion:

This study showed that approx 79.4% samples were positive for CHKV. To our knowledge, this is the first reported outbreak from last decades in which the presence of CHKV is confirmed in Karachi while affecting such large no. of individuals..

Conclusion:

CHKV diagnosis should be considered by the scientists and clinicians as a differential diagnosis in febrile patients, and appropriate control strategies must be adopted for its surveillance.

FUNDING STATEMENT

The author(s) received no specific funding for this work.

Keywords: Alphavirus; Togavirus; Chikungunya Fever; Pakistan.

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#Imipramine Inhibits #Chikungunya Virus #Replication in #Human Skin Fibroblasts through Interference with Intracellular Cholesterol Trafficking (Sci Rep., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Sci Rep. 2017 Jun 9;7(1):3145. doi: 10.1038/s41598-017-03316-5.

Imipramine Inhibits Chikungunya Virus Replication in Human Skin Fibroblasts through Interference with Intracellular Cholesterol Trafficking.

Wichit S1, Hamel R1, Bernard E2, Talignani L1, Diop F1, Ferraris P1, Liegeois F1, Ekchariyawat P3, Luplertlop N3, Surasombatpattana P4, Thomas F1, Merits A5, Choumet V6, Roques P7,8, Yssel H9, Briant L2, Missé D10.

Author information: 1 Laboratoire MIVEGEC, UMR 224 IRD/CNRS/UM1, Montpellier cedex 5, 34394, France. 2 Centre d’Étude d’Agents Pathogènes et Biotechnologies pour la Santé, CNRS-UMR 5236/UM, Montpellier cedex 5, 34293, France. 3 Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand. 4 Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkla, 90110, Thailand. 5 Institute of Technology, University of Tartu, Tartu, 50411, Estonia. 6 Environment and Infectious Risks Unit, Institut Pasteur, Paris, 75015, France. 7 CEA, iMETI, Division of Immuno-Virology, Université Paris Sud, Orsay, France. 8 Center for immunology of viral infections and autoimmune diseases Inserm, UMR 1184, Fontenay-aux-Roses, 91190, France. 9 Centre d’Immunologie et des Maladies Infectieuses, Inserm, U1135, Sorbonne Universités, UPMC, APHP Hôpital Pitié-Salpêtrière, Paris, 75013, France. 10 Laboratoire MIVEGEC, UMR 224 IRD/CNRS/UM1, Montpellier cedex 5, 34394, France. dorothee.misse@ird.fr.

 

Abstract

Chikungunya virus (CHIKV) is an emerging arbovirus of the Togaviridae family that poses a present worldwide threat to human in the absence of any licensed vaccine or antiviral treatment to control viral infection. Here, we show that compounds interfering with intracellular cholesterol transport have the capacity to inhibit CHIKV replication in human skin fibroblasts, a major viral entry site in the human host. Pretreatment of these cells with the class II cationic amphiphilic compound U18666A, or treatment with the FDA-approved antidepressant drug imipramine resulted in a near total inhibition of viral replication and production at the highest concentration used without any cytotoxic effects. Imipramine was found to affect both the fusion and replication steps of the viral life cycle. The key contribution of cholesterol availability to the CHIKV life cycle was validated further by the use of fibroblasts from Niemann-Pick type C (NPC) patients in which the virus was unable to replicate. Interestingly, imipramine also strongly inhibited the replication of several Flaviviridae family members, including Zika, West Nile and Dengue virus. Together, these data show that this compound is a potential drug candidate for anti-arboviral treatment.

PMID: 28600536 DOI: 10.1038/s41598-017-03316-5

Keywords: Imipramine; Togavirus; Zika Virus; Chikungunya Fever.

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