Coordination of Zika Virus Infection and Viroplasm Organization by Microtubules and Microtubule-Organizing Centers

Zika virus (ZIKV) became a global health concern in 2016 due to its links to congenital microcephaly and other birth defects. Flaviviruses, including ZIKV, reorganize the endoplasmic reticulum (ER) to form a viroplasm, a compartment where virus particles are assembled. Microtubules (MTs) and microtu...

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Main Authors: Rebecca A. Buchwalter, Sarah C. Ogden, Sara B. York, Li Sun, Chunfeng Zheng, Christy Hammack, Yichen Cheng, Jieyan V. Chen, Allaura S. Cone, David G. Meckes, Hengli Tang, Timothy L. Megraw
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/10/12/3335
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author Rebecca A. Buchwalter
Sarah C. Ogden
Sara B. York
Li Sun
Chunfeng Zheng
Christy Hammack
Yichen Cheng
Jieyan V. Chen
Allaura S. Cone
David G. Meckes
Hengli Tang
Timothy L. Megraw
author_facet Rebecca A. Buchwalter
Sarah C. Ogden
Sara B. York
Li Sun
Chunfeng Zheng
Christy Hammack
Yichen Cheng
Jieyan V. Chen
Allaura S. Cone
David G. Meckes
Hengli Tang
Timothy L. Megraw
author_sort Rebecca A. Buchwalter
collection DOAJ
description Zika virus (ZIKV) became a global health concern in 2016 due to its links to congenital microcephaly and other birth defects. Flaviviruses, including ZIKV, reorganize the endoplasmic reticulum (ER) to form a viroplasm, a compartment where virus particles are assembled. Microtubules (MTs) and microtubule-organizing centers (MTOCs) coordinate structural and trafficking functions in the cell, and MTs also support replication of flaviviruses. Here we investigated the roles of MTs and the cell’s MTOCs on ZIKV viroplasm organization and virus production. We show that a toroidal-shaped viroplasm forms upon ZIKV infection, and MTs are organized at the viroplasm core and surrounding the viroplasm. We show that MTs are necessary for viroplasm organization and impact infectious virus production. In addition, the centrosome and the Golgi MTOC are closely associated with the viroplasm, and the centrosome coordinates the organization of the ZIKV viroplasm toroidal structure. Surprisingly, viroplasm formation and virus production are not significantly impaired when infected cells have no centrosomes and impaired Golgi MTOC, and we show that MTs are anchored to the viroplasm surface in these cells. We propose that the viroplasm is a site of MT organization, and the MTs organized at the viroplasm are sufficient for efficient virus production.
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spelling doaj.art-303032ca97c04348983879c035ca9e8f2023-11-23T07:36:22ZengMDPI AGCells2073-44092021-11-011012333510.3390/cells10123335Coordination of Zika Virus Infection and Viroplasm Organization by Microtubules and Microtubule-Organizing CentersRebecca A. Buchwalter0Sarah C. Ogden1Sara B. York2Li Sun3Chunfeng Zheng4Christy Hammack5Yichen Cheng6Jieyan V. Chen7Allaura S. Cone8David G. Meckes9Hengli Tang10Timothy L. Megraw11Department of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, USADepartment of Biological Science, Florida State University, Tallahassee, FL 32306, USADepartment of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, USADepartment of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, USADepartment of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, USADepartment of Biological Science, Florida State University, Tallahassee, FL 32306, USADepartment of Biological Science, Florida State University, Tallahassee, FL 32306, USADepartment of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, USADepartment of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, USADepartment of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, USADepartment of Biological Science, Florida State University, Tallahassee, FL 32306, USADepartment of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, USAZika virus (ZIKV) became a global health concern in 2016 due to its links to congenital microcephaly and other birth defects. Flaviviruses, including ZIKV, reorganize the endoplasmic reticulum (ER) to form a viroplasm, a compartment where virus particles are assembled. Microtubules (MTs) and microtubule-organizing centers (MTOCs) coordinate structural and trafficking functions in the cell, and MTs also support replication of flaviviruses. Here we investigated the roles of MTs and the cell’s MTOCs on ZIKV viroplasm organization and virus production. We show that a toroidal-shaped viroplasm forms upon ZIKV infection, and MTs are organized at the viroplasm core and surrounding the viroplasm. We show that MTs are necessary for viroplasm organization and impact infectious virus production. In addition, the centrosome and the Golgi MTOC are closely associated with the viroplasm, and the centrosome coordinates the organization of the ZIKV viroplasm toroidal structure. Surprisingly, viroplasm formation and virus production are not significantly impaired when infected cells have no centrosomes and impaired Golgi MTOC, and we show that MTs are anchored to the viroplasm surface in these cells. We propose that the viroplasm is a site of MT organization, and the MTs organized at the viroplasm are sufficient for efficient virus production.https://www.mdpi.com/2073-4409/10/12/3335Zika virusZIKVflaviviruscentrosomecentriolemicrotubule-organizing center
spellingShingle Rebecca A. Buchwalter
Sarah C. Ogden
Sara B. York
Li Sun
Chunfeng Zheng
Christy Hammack
Yichen Cheng
Jieyan V. Chen
Allaura S. Cone
David G. Meckes
Hengli Tang
Timothy L. Megraw
Coordination of Zika Virus Infection and Viroplasm Organization by Microtubules and Microtubule-Organizing Centers
Cells
Zika virus
ZIKV
flavivirus
centrosome
centriole
microtubule-organizing center
title Coordination of Zika Virus Infection and Viroplasm Organization by Microtubules and Microtubule-Organizing Centers
title_full Coordination of Zika Virus Infection and Viroplasm Organization by Microtubules and Microtubule-Organizing Centers
title_fullStr Coordination of Zika Virus Infection and Viroplasm Organization by Microtubules and Microtubule-Organizing Centers
title_full_unstemmed Coordination of Zika Virus Infection and Viroplasm Organization by Microtubules and Microtubule-Organizing Centers
title_short Coordination of Zika Virus Infection and Viroplasm Organization by Microtubules and Microtubule-Organizing Centers
title_sort coordination of zika virus infection and viroplasm organization by microtubules and microtubule organizing centers
topic Zika virus
ZIKV
flavivirus
centrosome
centriole
microtubule-organizing center
url https://www.mdpi.com/2073-4409/10/12/3335
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