Differential Transmission of Antiviral Drug-Resistant Chikungunya Viruses by <italic toggle="yes">Aedes</italic> Mosquitoes

ABSTRACT The chikungunya virus (CHIKV) is transmitted by female Aedes aegypti and Aedes albopictus mosquitoes, mostly present in (sub)tropical regions. No antivirals are available to treat CHIKV infections. If antiviral drugs are proven efficient to treat CHIKV-infected patients, it will be pivotal...

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Autores principales:	Leen Delang, Pei-Shi Yen, Thomas Vallet, Marie Vazeille, Marco Vignuzzi, Anna-Bella Failloux
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Aedes antiviral agents chikungunya virus drug resistance mosquito transmission Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ee0324e1478e467a8b8518847568bd9f
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spelling	oai:doaj.org-article:ee0324e1478e467a8b8518847568bd9f2021-11-15T15:25:50ZDifferential Transmission of Antiviral Drug-Resistant Chikungunya Viruses by <italic toggle="yes">Aedes</italic> Mosquitoes10.1128/mSphere.00230-182379-5042https://doaj.org/article/ee0324e1478e467a8b8518847568bd9f2018-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00230-18https://doaj.org/toc/2379-5042ABSTRACT The chikungunya virus (CHIKV) is transmitted by female Aedes aegypti and Aedes albopictus mosquitoes, mostly present in (sub)tropical regions. No antivirals are available to treat CHIKV infections. If antiviral drugs are proven efficient to treat CHIKV-infected patients, it will be pivotal to determine whether drug-resistant viruses can be transmitted from one human to another by their mosquito vectors. We orally infected Aedes aegypti mosquitoes with a blood meal containing wild-type or drug-resistant CHIKV variants (i.e., MADTPres CHIKV, with mutation in the nsP1 gene, and T-705res CHIKV, with mutation in the RNA-dependent RNA polymerase [RdRp] gene). Viral loads were quantified in bodies (infection), heads (dissemination), and saliva (transmission) of individual mosquitoes. The infection rate of the resistant viruses was similar to that of the wild-type virus. However, the dissemination of T-705res CHIKV was markedly decreased compared to wild-type and MADTPres CHIKV. Furthermore, T-705res CHIKV was only transmitted in the saliva at day 20 postinfection (p.i.), whereas transmission of wild-type CHIKV was observed at day 3 p.i. The attenuated phenotype of the T-705res virus was confirmed in mosquito cell culture, whereas the replication fitness in Vero cells was similar to that of the wild type. In bodies and heads of mosquitoes infected with the resistant variants, the resistant phenotype and genotype were retained. Also in the saliva, the resistant genotype of MADTPres CHIKV was maintained. Our results illustrate that the fitness of drug-resistant variants should be evaluated in both hosts to be able to select antiviral drugs with a limited risk for the spread of drug resistance by mosquitoes. IMPORTANCE Because of its global reemergence and unusual morbidities associated with infection, the chikungunya virus (CHIKV) has become a substantial public health problem. However, no antivirals are currently available to treat CHIKV infections. If antiviral drugs will prove to be efficient to treat CHIKV-infected patients, it will be essential to understand if drug-resistant viruses can be transmitted from one human to another by the mosquito. We therefore orally infected Aedes mosquitoes with drug-resistant CHIKV variants and determined the replication and transmission levels. One of the antiviral drug-resistant CHIKV variants could efficiently replicate and disseminate in both laboratory and field-collected mosquitoes. In addition, this variant retained its drug-resistant genotype in the saliva. In contrast, the other drug-resistant variant was markedly attenuated in mosquitoes. Our results illustrate that extra caution for drug resistance should be considered when developing an antiarbovirus antiviral in order to minimize the risk of spreading drug resistance by mosquitoes.Leen DelangPei-Shi YenThomas ValletMarie VazeilleMarco VignuzziAnna-Bella FaillouxAmerican Society for MicrobiologyarticleAedesantiviral agentschikungunya virusdrug resistancemosquitotransmissionMicrobiologyQR1-502ENmSphere, Vol 3, Iss 4 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Aedes antiviral agents chikungunya virus drug resistance mosquito transmission Microbiology QR1-502
spellingShingle	Aedes antiviral agents chikungunya virus drug resistance mosquito transmission Microbiology QR1-502 Leen Delang Pei-Shi Yen Thomas Vallet Marie Vazeille Marco Vignuzzi Anna-Bella Failloux Differential Transmission of Antiviral Drug-Resistant Chikungunya Viruses by <italic toggle="yes">Aedes</italic> Mosquitoes
description	ABSTRACT The chikungunya virus (CHIKV) is transmitted by female Aedes aegypti and Aedes albopictus mosquitoes, mostly present in (sub)tropical regions. No antivirals are available to treat CHIKV infections. If antiviral drugs are proven efficient to treat CHIKV-infected patients, it will be pivotal to determine whether drug-resistant viruses can be transmitted from one human to another by their mosquito vectors. We orally infected Aedes aegypti mosquitoes with a blood meal containing wild-type or drug-resistant CHIKV variants (i.e., MADTPres CHIKV, with mutation in the nsP1 gene, and T-705res CHIKV, with mutation in the RNA-dependent RNA polymerase [RdRp] gene). Viral loads were quantified in bodies (infection), heads (dissemination), and saliva (transmission) of individual mosquitoes. The infection rate of the resistant viruses was similar to that of the wild-type virus. However, the dissemination of T-705res CHIKV was markedly decreased compared to wild-type and MADTPres CHIKV. Furthermore, T-705res CHIKV was only transmitted in the saliva at day 20 postinfection (p.i.), whereas transmission of wild-type CHIKV was observed at day 3 p.i. The attenuated phenotype of the T-705res virus was confirmed in mosquito cell culture, whereas the replication fitness in Vero cells was similar to that of the wild type. In bodies and heads of mosquitoes infected with the resistant variants, the resistant phenotype and genotype were retained. Also in the saliva, the resistant genotype of MADTPres CHIKV was maintained. Our results illustrate that the fitness of drug-resistant variants should be evaluated in both hosts to be able to select antiviral drugs with a limited risk for the spread of drug resistance by mosquitoes. IMPORTANCE Because of its global reemergence and unusual morbidities associated with infection, the chikungunya virus (CHIKV) has become a substantial public health problem. However, no antivirals are currently available to treat CHIKV infections. If antiviral drugs will prove to be efficient to treat CHIKV-infected patients, it will be essential to understand if drug-resistant viruses can be transmitted from one human to another by the mosquito. We therefore orally infected Aedes mosquitoes with drug-resistant CHIKV variants and determined the replication and transmission levels. One of the antiviral drug-resistant CHIKV variants could efficiently replicate and disseminate in both laboratory and field-collected mosquitoes. In addition, this variant retained its drug-resistant genotype in the saliva. In contrast, the other drug-resistant variant was markedly attenuated in mosquitoes. Our results illustrate that extra caution for drug resistance should be considered when developing an antiarbovirus antiviral in order to minimize the risk of spreading drug resistance by mosquitoes.
format	article
author	Leen Delang Pei-Shi Yen Thomas Vallet Marie Vazeille Marco Vignuzzi Anna-Bella Failloux
author_facet	Leen Delang Pei-Shi Yen Thomas Vallet Marie Vazeille Marco Vignuzzi Anna-Bella Failloux
author_sort	Leen Delang
title	Differential Transmission of Antiviral Drug-Resistant Chikungunya Viruses by <italic toggle="yes">Aedes</italic> Mosquitoes
title_short	Differential Transmission of Antiviral Drug-Resistant Chikungunya Viruses by <italic toggle="yes">Aedes</italic> Mosquitoes
title_full	Differential Transmission of Antiviral Drug-Resistant Chikungunya Viruses by <italic toggle="yes">Aedes</italic> Mosquitoes
title_fullStr	Differential Transmission of Antiviral Drug-Resistant Chikungunya Viruses by <italic toggle="yes">Aedes</italic> Mosquitoes
title_full_unstemmed	Differential Transmission of Antiviral Drug-Resistant Chikungunya Viruses by <italic toggle="yes">Aedes</italic> Mosquitoes
title_sort	differential transmission of antiviral drug-resistant chikungunya viruses by <italic toggle="yes">aedes</italic> mosquitoes
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/ee0324e1478e467a8b8518847568bd9f
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Differential Transmission of Antiviral Drug-Resistant Chikungunya Viruses by <italic toggle="yes">Aedes</italic> Mosquitoes

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