Contemporary Zika Virus Isolates Induce More dsRNA and Produce More Negative-Strand Intermediate in Human Astrocytoma Cells

The recent emergence and rapid geographic expansion of Zika virus (ZIKV) poses a significant challenge for public health. Although historically causing only mild febrile illness, recent ZIKV outbreaks have been associated with more severe neurological complications, such as Guillain-Barré s...

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Asıl Yazarlar: Trisha R. Barnard, Maaran M. Rajah, Selena M. Sagan
Materyal Türü: Makale
Dil:English
Baskı/Yayın Bilgisi: MDPI AG 2018-12-01
Seri Bilgileri:Viruses
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Online Erişim:https://www.mdpi.com/1999-4915/10/12/728
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author Trisha R. Barnard
Maaran M. Rajah
Selena M. Sagan
author_facet Trisha R. Barnard
Maaran M. Rajah
Selena M. Sagan
author_sort Trisha R. Barnard
collection DOAJ
description The recent emergence and rapid geographic expansion of Zika virus (ZIKV) poses a significant challenge for public health. Although historically causing only mild febrile illness, recent ZIKV outbreaks have been associated with more severe neurological complications, such as Guillain-Barré syndrome and fetal microcephaly. Here we demonstrate that two contemporary (2015) ZIKV isolates from Puerto Rico and Brazil may have increased replicative fitness in human astrocytoma cells. Over a single infectious cycle, the Brazilian isolate replicates to higher titers and induces more severe cytopathic effects in human astrocytoma cells than the historical African reference strain or an early Asian lineage isolate. In addition, both contemporary isolates induce significantly more double-stranded RNA in infected astrocytoma cells, despite similar numbers of infected cells across isolates. Moreover, when we quantified positive- and negative-strand viral RNA, we found that the Asian lineage isolates displayed substantially more negative-strand replicative intermediates than the African lineage isolate in human astrocytoma cells. However, over multiple rounds of infection, the contemporary ZIKV isolates appear to be impaired in cell spread, infecting a lower proportion of cells at a low MOI despite replicating to similar or higher titers. Taken together, our data suggests that contemporary ZIKV isolates may have evolved mechanisms that allow them to replicate with increased efficiency in certain cell types, thereby highlighting the importance of cell-intrinsic factors in studies of viral replicative fitness.
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spelling doaj.art-80e53ed4aa1741aca37f032dba2c94d22022-12-22T00:11:04ZengMDPI AGViruses1999-49152018-12-01101272810.3390/v10120728v10120728Contemporary Zika Virus Isolates Induce More dsRNA and Produce More Negative-Strand Intermediate in Human Astrocytoma CellsTrisha R. Barnard0Maaran M. Rajah1Selena M. Sagan2Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, CanadaDepartment of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, CanadaDepartment of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, CanadaThe recent emergence and rapid geographic expansion of Zika virus (ZIKV) poses a significant challenge for public health. Although historically causing only mild febrile illness, recent ZIKV outbreaks have been associated with more severe neurological complications, such as Guillain-Barré syndrome and fetal microcephaly. Here we demonstrate that two contemporary (2015) ZIKV isolates from Puerto Rico and Brazil may have increased replicative fitness in human astrocytoma cells. Over a single infectious cycle, the Brazilian isolate replicates to higher titers and induces more severe cytopathic effects in human astrocytoma cells than the historical African reference strain or an early Asian lineage isolate. In addition, both contemporary isolates induce significantly more double-stranded RNA in infected astrocytoma cells, despite similar numbers of infected cells across isolates. Moreover, when we quantified positive- and negative-strand viral RNA, we found that the Asian lineage isolates displayed substantially more negative-strand replicative intermediates than the African lineage isolate in human astrocytoma cells. However, over multiple rounds of infection, the contemporary ZIKV isolates appear to be impaired in cell spread, infecting a lower proportion of cells at a low MOI despite replicating to similar or higher titers. Taken together, our data suggests that contemporary ZIKV isolates may have evolved mechanisms that allow them to replicate with increased efficiency in certain cell types, thereby highlighting the importance of cell-intrinsic factors in studies of viral replicative fitness.https://www.mdpi.com/1999-4915/10/12/728Zika virusflavivirusastrocytomasdsRNAviral fitness
spellingShingle Trisha R. Barnard
Maaran M. Rajah
Selena M. Sagan
Contemporary Zika Virus Isolates Induce More dsRNA and Produce More Negative-Strand Intermediate in Human Astrocytoma Cells
Viruses
Zika virus
flavivirus
astrocytomas
dsRNA
viral fitness
title Contemporary Zika Virus Isolates Induce More dsRNA and Produce More Negative-Strand Intermediate in Human Astrocytoma Cells
title_full Contemporary Zika Virus Isolates Induce More dsRNA and Produce More Negative-Strand Intermediate in Human Astrocytoma Cells
title_fullStr Contemporary Zika Virus Isolates Induce More dsRNA and Produce More Negative-Strand Intermediate in Human Astrocytoma Cells
title_full_unstemmed Contemporary Zika Virus Isolates Induce More dsRNA and Produce More Negative-Strand Intermediate in Human Astrocytoma Cells
title_short Contemporary Zika Virus Isolates Induce More dsRNA and Produce More Negative-Strand Intermediate in Human Astrocytoma Cells
title_sort contemporary zika virus isolates induce more dsrna and produce more negative strand intermediate in human astrocytoma cells
topic Zika virus
flavivirus
astrocytomas
dsRNA
viral fitness
url https://www.mdpi.com/1999-4915/10/12/728
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