The distinguishing NS5-M114V mutation in American Zika virus isolates has negligible impacts on virus replication and transmission potential

During 2015-2016, outbreaks of Zika virus (ZIKV) occurred in Southeast Asia and the Americas. Most ZIKV infections in humans are asymptomatic, while clinical manifestation is usually a self-limiting febrile disease with maculopapular rash. However, ZIKV is capable of inducing a range of severe neuro...

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Published inPLoS neglected tropical diseases Vol. 16; no. 5; p. e0010426
Main Authors Peng, Nias Y G, Amarilla, Alberto A, Hugo, Leon E, Modhiran, Naphak, Sng, Julian D J, Slonchak, Andrii, Watterson, Daniel, Setoh, Yin Xiang, Khromykh, Alexander A
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 01.05.2022
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Abstract During 2015-2016, outbreaks of Zika virus (ZIKV) occurred in Southeast Asia and the Americas. Most ZIKV infections in humans are asymptomatic, while clinical manifestation is usually a self-limiting febrile disease with maculopapular rash. However, ZIKV is capable of inducing a range of severe neurological complications collectively described as congenital Zika syndrome (CZS). Notably, the scale and magnitude of outbreaks in Southeast Asia were significantly smaller compared to those in the Americas. Sequence comparison between epidemic-associated ZIKV strains from Southeast Asia with those from the Americas revealed a methionine to valine substitution at residue position 114 of the NS5 protein (NS5-M114V) in all the American isolates. Using an American isolate of ZIKV (Natal), we investigated the impact of NS5-M114V mutation on virus replication in cells, virulence in interferon (IFN) α/β receptor knockout (Ifnar-/-) mice, as well as replication and transmission potential in Aedes aegypti mosquitoes. We demonstrated that NS5-M114V mutation had insignificant effect on ZIKV replication efficiency in cells, its ability to degrade STAT2, and virulence in vivo, albeit viremia was slightly prolonged in mice. Furthermore, NS5-M114V mutation decreased mosquito infection and dissemination rates but had no effect on virus secretion into the saliva. Taken together, our findings support the notion that NS5-M114V mutation is unlikely to be a major determinant for virus replication and transmission potential.
AbstractList During 2015-2016, outbreaks of Zika virus (ZIKV) occurred in Southeast Asia and the Americas. Most ZIKV infections in humans are asymptomatic, while clinical manifestation is usually a self-limiting febrile disease with maculopapular rash. However, ZIKV is capable of inducing a range of severe neurological complications collectively described as congenital Zika syndrome (CZS). Notably, the scale and magnitude of outbreaks in Southeast Asia were significantly smaller compared to those in the Americas. Sequence comparison between epidemic-associated ZIKV strains from Southeast Asia with those from the Americas revealed a methionine to valine substitution at residue position 114 of the NS5 protein (NS5-M114V) in all the American isolates. Using an American isolate of ZIKV (Natal), we investigated the impact of NS5-M114V mutation on virus replication in cells, virulence in interferon (IFN) α/β receptor knockout (Ifnar-/-) mice, as well as replication and transmission potential in Aedes aegypti mosquitoes. We demonstrated that NS5-M114V mutation had insignificant effect on ZIKV replication efficiency in cells, its ability to degrade STAT2, and virulence in vivo, albeit viremia was slightly prolonged in mice. Furthermore, NS5-M114V mutation decreased mosquito infection and dissemination rates but had no effect on virus secretion into the saliva. Taken together, our findings support the notion that NS5-M114V mutation is unlikely to be a major determinant for virus replication and transmission potential.
During 2015–2016, outbreaks of Zika virus (ZIKV) occurred in Southeast Asia and the Americas. Most ZIKV infections in humans are asymptomatic, while clinical manifestation is usually a self-limiting febrile disease with maculopapular rash. However, ZIKV is capable of inducing a range of severe neurological complications collectively described as congenital Zika syndrome (CZS). Notably, the scale and magnitude of outbreaks in Southeast Asia were significantly smaller compared to those in the Americas. Sequence comparison between epidemic-associated ZIKV strains from Southeast Asia with those from the Americas revealed a methionine to valine substitution at residue position 114 of the NS5 protein (NS5-M114V) in all the American isolates. Using an American isolate of ZIKV (Natal), we investigated the impact of NS5-M114V mutation on virus replication in cells, virulence in interferon (IFN) α/β receptor knockout ( Ifnar -/- ) mice, as well as replication and transmission potential in Aedes aegypti mosquitoes. We demonstrated that NS5-M114V mutation had insignificant effect on ZIKV replication efficiency in cells, its ability to degrade STAT2, and virulence in vivo , albeit viremia was slightly prolonged in mice. Furthermore, NS5-M114V mutation decreased mosquito infection and dissemination rates but had no effect on virus secretion into the saliva. Taken together, our findings support the notion that NS5-M114V mutation is unlikely to be a major determinant for virus replication and transmission potential. Zika virus (ZIKV) emerged to cause outbreaks in Southeast Asia and the Americas during 2015–2016. However, the scale of outbreaks in Southeast Asia were significantly smaller compared to epidemic in the Americas. A methionine to valine amino acid mutation at residue position 114 of the NS5 protein (NS5-M114V) is hypothesized to influence the epidemic outcomes of ZIKV, which led to the large-scale epidemic that occurred in the Americas. By analyzing infection of mammalian and mosquito cells, IFNα/β receptor knockout ( Ifnar -/- ) mice and Aedes aegypti mosquitoes with engineered ZIKV isolates containing either methionine or valine at residue position 114 of the NS5 protein, we demonstrated that the NS5-M114V mutation did not affect virus replication efficiency and STAT2 degradation in cells, virulence in mice, or virus secretion into the mosquito saliva. The NS5-M114V mutation slightly prolonged viremia in Ifnar -/- mice and reduced mosquito infection rate. Collectively, our findings suggest that the NS5-M114V mutation is unlikely to have significantly influenced the ZIKV epidemic in the Americas.
During 2015–2016, outbreaks of Zika virus (ZIKV) occurred in Southeast Asia and the Americas. Most ZIKV infections in humans are asymptomatic, while clinical manifestation is usually a self-limiting febrile disease with maculopapular rash. However, ZIKV is capable of inducing a range of severe neurological complications collectively described as congenital Zika syndrome (CZS). Notably, the scale and magnitude of outbreaks in Southeast Asia were significantly smaller compared to those in the Americas. Sequence comparison between epidemic-associated ZIKV strains from Southeast Asia with those from the Americas revealed a methionine to valine substitution at residue position 114 of the NS5 protein (NS5-M114V) in all the American isolates. Using an American isolate of ZIKV (Natal), we investigated the impact of NS5-M114V mutation on virus replication in cells, virulence in interferon (IFN) α/β receptor knockout ( Ifnar -/- ) mice, as well as replication and transmission potential in Aedes aegypti mosquitoes. We demonstrated that NS5-M114V mutation had insignificant effect on ZIKV replication efficiency in cells, its ability to degrade STAT2, and virulence in vivo , albeit viremia was slightly prolonged in mice. Furthermore, NS5-M114V mutation decreased mosquito infection and dissemination rates but had no effect on virus secretion into the saliva. Taken together, our findings support the notion that NS5-M114V mutation is unlikely to be a major determinant for virus replication and transmission potential.
During 2015-2016, outbreaks of Zika virus (ZIKV) occurred in Southeast Asia and the Americas. Most ZIKV infections in humans are asymptomatic, while clinical manifestation is usually a self-limiting febrile disease with maculopapular rash. However, ZIKV is capable of inducing a range of severe neurological complications collectively described as congenital Zika syndrome (CZS). Notably, the scale and magnitude of outbreaks in Southeast Asia were significantly smaller compared to those in the Americas. Sequence comparison between epidemic-associated ZIKV strains from Southeast Asia with those from the Americas revealed a methionine to valine substitution at residue position 114 of the NS5 protein (NS5-M114V) in all the American isolates. Using an American isolate of ZIKV (Natal), we investigated the impact of NS5-M114V mutation on virus replication in cells, virulence in interferon (IFN) [alpha]/[beta] receptor knockout (Ifnar.sup.-/-) mice, as well as replication and transmission potential in Aedes aegypti mosquitoes. We demonstrated that NS5-M114V mutation had insignificant effect on ZIKV replication efficiency in cells, its ability to degrade STAT2, and virulence in vivo, albeit viremia was slightly prolonged in mice. Furthermore, NS5-M114V mutation decreased mosquito infection and dissemination rates but had no effect on virus secretion into the saliva. Taken together, our findings support the notion that NS5-M114V mutation is unlikely to be a major determinant for virus replication and transmission potential.
Audience Academic
Author Setoh, Yin Xiang
Peng, Nias Y G
Hugo, Leon E
Modhiran, Naphak
Slonchak, Andrii
Amarilla, Alberto A
Khromykh, Alexander A
Sng, Julian D J
Watterson, Daniel
AuthorAffiliation 2 Mosquito Control Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia
1 School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Queensland, Australia
3 Australian Infectious Diseases Research Centre, Global Virus Network Centre of Excellence, Queensland, Brisbane, Australia
WRAIR, UNITED STATES
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/35536870$$D View this record in MEDLINE/PubMed
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Current address: Environmental Health Institute, National Environment Agency, Singapore
The authors have declared that no competing interests exist.
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Snippet During 2015-2016, outbreaks of Zika virus (ZIKV) occurred in Southeast Asia and the Americas. Most ZIKV infections in humans are asymptomatic, while clinical...
During 2015–2016, outbreaks of Zika virus (ZIKV) occurred in Southeast Asia and the Americas. Most ZIKV infections in humans are asymptomatic, while clinical...
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StartPage e0010426
SubjectTerms Amino acids
Analysis
Aquatic insects
Biological response modifiers
Biology and Life Sciences
Cells
Complications
Epidemics
Gene mutations
Genomes
Infections
Interferon
Medicine and Health Sciences
Methionine
Microbiological strains
Mosquitoes
Mutagenesis
Mutation
Neurological complications
NS5 protein
Nucleotide sequence
Outbreaks
People and Places
Proteins
Receptors
Replication
Saliva
Secretion
Stat2 protein
Strains
Transmission
Tropical diseases
Valine
Vector-borne diseases
Viremia
Virulence
Viruses
Zika virus
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Title The distinguishing NS5-M114V mutation in American Zika virus isolates has negligible impacts on virus replication and transmission potential
URI https://www.ncbi.nlm.nih.gov/pubmed/35536870
https://www.proquest.com/docview/2677644848
https://search.proquest.com/docview/2661952637
https://pubmed.ncbi.nlm.nih.gov/PMC9122223
https://doaj.org/article/7141cec143c44df099b8a86caa25b5fa
http://dx.doi.org/10.1371/journal.pntd.0010426
Volume 16
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