<italic toggle="yes">Wolbachia w</italic>Stri Blocks Zika Virus Growth at Two Independent Stages of Viral Replication

ABSTRACT Mosquito-transmitted viruses are spread globally and present a great risk to human health. Among the many approaches investigated to limit the diseases caused by these viruses are attempts to make mosquitos resistant to virus infection. Coinfection of mosquitos with the bacterium Wolbachia...

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Autores principales:	M. J. Schultz, A. L. Tan, C. N. Gray, S. Isern, S. F. Michael, H. M. Frydman, J. H. Connor
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Wolbachia arbovirus arthropod vectors biocontrol mechanisms of action Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/f380826ae58d437db671d89c1ad40da0
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spelling	oai:doaj.org-article:f380826ae58d437db671d89c1ad40da02021-11-15T16:00:24Z<italic toggle="yes">Wolbachia w</italic>Stri Blocks Zika Virus Growth at Two Independent Stages of Viral Replication10.1128/mBio.00738-182150-7511https://doaj.org/article/f380826ae58d437db671d89c1ad40da02018-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00738-18https://doaj.org/toc/2150-7511ABSTRACT Mosquito-transmitted viruses are spread globally and present a great risk to human health. Among the many approaches investigated to limit the diseases caused by these viruses are attempts to make mosquitos resistant to virus infection. Coinfection of mosquitos with the bacterium Wolbachia pipientis from supergroup A is a recent strategy employed to reduce the capacity for major vectors in the Aedes mosquito genus to transmit viruses, including dengue virus (DENV), Chikungunya virus (CHIKV), and Zika virus (ZIKV). Recently, a supergroup B Wolbachia wStri, isolated from Laodelphax striatellus, was shown to inhibit multiple lineages of ZIKV in Aedes albopictus cells. Here, we show that wStri blocks the growth of positive-sense RNA viruses DENV, CHIKV, ZIKV, and yellow fever virus by greater than 99.9%. wStri presence did not affect the growth of the negative-sense RNA viruses LaCrosse virus or vesicular stomatitis virus. Investigation of the stages of the ZIKV life cycle inhibited by wStri identified two distinct blocks in viral replication. We found a reduction of ZIKV entry into wStri-infected cells. This was partially rescued by the addition of a cholesterol-lipid supplement. Independent of entry, transfected viral genome was unable to replicate in Wolbachia-infected cells. RNA transfection and metabolic labeling studies suggested that this replication defect is at the level of RNA translation, where we saw a 66% reduction in mosquito protein synthesis in wStri-infected cells. This study’s findings increase the potential for application of wStri to block additional arboviruses and also identify specific blocks in viral infection caused by Wolbachia coinfection. IMPORTANCE Dengue, Zika, and yellow fever viruses are mosquito-transmitted diseases that have spread throughout the world, causing millions of infections and thousands of deaths each year. Existing programs that seek to contain these diseases through elimination of the mosquito population have so far failed, making it crucial to explore new ways of limiting the spread of these viruses. Here, we show that introduction of an insect symbiont, Wolbachia wStri, into mosquito cells is highly effective at reducing yellow fever virus, dengue virus, Zika virus, and Chikungunya virus production. Reduction of virus replication was attributable to decreases in entry and a strong block of virus gene expression at the translational level. These findings expand the potential use of Wolbachia wStri to block viruses and identify two separate steps for limiting virus replication in mosquitos that could be targeted via microbes or other means as an antiviral strategy.M. J. SchultzA. L. TanC. N. GrayS. IsernS. F. MichaelH. M. FrydmanJ. H. ConnorAmerican Society for MicrobiologyarticleWolbachiaarbovirusarthropod vectorsbiocontrolmechanisms of actionMicrobiologyQR1-502ENmBio, Vol 9, Iss 3 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Wolbachia arbovirus arthropod vectors biocontrol mechanisms of action Microbiology QR1-502
spellingShingle	Wolbachia arbovirus arthropod vectors biocontrol mechanisms of action Microbiology QR1-502 M. J. Schultz A. L. Tan C. N. Gray S. Isern S. F. Michael H. M. Frydman J. H. Connor <italic toggle="yes">Wolbachia w</italic>Stri Blocks Zika Virus Growth at Two Independent Stages of Viral Replication
description	ABSTRACT Mosquito-transmitted viruses are spread globally and present a great risk to human health. Among the many approaches investigated to limit the diseases caused by these viruses are attempts to make mosquitos resistant to virus infection. Coinfection of mosquitos with the bacterium Wolbachia pipientis from supergroup A is a recent strategy employed to reduce the capacity for major vectors in the Aedes mosquito genus to transmit viruses, including dengue virus (DENV), Chikungunya virus (CHIKV), and Zika virus (ZIKV). Recently, a supergroup B Wolbachia wStri, isolated from Laodelphax striatellus, was shown to inhibit multiple lineages of ZIKV in Aedes albopictus cells. Here, we show that wStri blocks the growth of positive-sense RNA viruses DENV, CHIKV, ZIKV, and yellow fever virus by greater than 99.9%. wStri presence did not affect the growth of the negative-sense RNA viruses LaCrosse virus or vesicular stomatitis virus. Investigation of the stages of the ZIKV life cycle inhibited by wStri identified two distinct blocks in viral replication. We found a reduction of ZIKV entry into wStri-infected cells. This was partially rescued by the addition of a cholesterol-lipid supplement. Independent of entry, transfected viral genome was unable to replicate in Wolbachia-infected cells. RNA transfection and metabolic labeling studies suggested that this replication defect is at the level of RNA translation, where we saw a 66% reduction in mosquito protein synthesis in wStri-infected cells. This study’s findings increase the potential for application of wStri to block additional arboviruses and also identify specific blocks in viral infection caused by Wolbachia coinfection. IMPORTANCE Dengue, Zika, and yellow fever viruses are mosquito-transmitted diseases that have spread throughout the world, causing millions of infections and thousands of deaths each year. Existing programs that seek to contain these diseases through elimination of the mosquito population have so far failed, making it crucial to explore new ways of limiting the spread of these viruses. Here, we show that introduction of an insect symbiont, Wolbachia wStri, into mosquito cells is highly effective at reducing yellow fever virus, dengue virus, Zika virus, and Chikungunya virus production. Reduction of virus replication was attributable to decreases in entry and a strong block of virus gene expression at the translational level. These findings expand the potential use of Wolbachia wStri to block viruses and identify two separate steps for limiting virus replication in mosquitos that could be targeted via microbes or other means as an antiviral strategy.
format	article
author	M. J. Schultz A. L. Tan C. N. Gray S. Isern S. F. Michael H. M. Frydman J. H. Connor
author_facet	M. J. Schultz A. L. Tan C. N. Gray S. Isern S. F. Michael H. M. Frydman J. H. Connor
author_sort	M. J. Schultz
title	<italic toggle="yes">Wolbachia w</italic>Stri Blocks Zika Virus Growth at Two Independent Stages of Viral Replication
title_short	<italic toggle="yes">Wolbachia w</italic>Stri Blocks Zika Virus Growth at Two Independent Stages of Viral Replication
title_full	<italic toggle="yes">Wolbachia w</italic>Stri Blocks Zika Virus Growth at Two Independent Stages of Viral Replication
title_fullStr	<italic toggle="yes">Wolbachia w</italic>Stri Blocks Zika Virus Growth at Two Independent Stages of Viral Replication
title_full_unstemmed	<italic toggle="yes">Wolbachia w</italic>Stri Blocks Zika Virus Growth at Two Independent Stages of Viral Replication
title_sort	<italic toggle="yes">wolbachia w</italic>stri blocks zika virus growth at two independent stages of viral replication
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/f380826ae58d437db671d89c1ad40da0
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<italic toggle="yes">Wolbachia w</italic>Stri Blocks Zika Virus Growth at Two Independent Stages of Viral Replication

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