Viral Entry Properties Required for Fitness in Humans Are Lost through Rapid Genomic Change during Viral Isolation
IMPORTANCE Human parainfluenza virus 3 is an important cause of morbidity and mortality among infants, the immunocompromised, and the elderly. Using deep genomic sequencing of HPIV-3-positive clinical material and its subsequent viral isolate, we discover a number of known and novel coding mutations...
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American Society for Microbiology
2018
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oai:doaj.org-article:116787510a404c218ec29e3d5ebc31b92021-11-15T16:00:15ZViral Entry Properties Required for Fitness in Humans Are Lost through Rapid Genomic Change during Viral Isolation10.1128/mBio.00898-182150-7511https://doaj.org/article/116787510a404c218ec29e3d5ebc31b92018-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00898-18https://doaj.org/toc/2150-7511IMPORTANCE Human parainfluenza virus 3 is an important cause of morbidity and mortality among infants, the immunocompromised, and the elderly. Using deep genomic sequencing of HPIV-3-positive clinical material and its subsequent viral isolate, we discover a number of known and novel coding mutations in the main HPIV-3 attachment protein HN during brief exposure to immortalized cells. These mutations significantly alter function of the fusion complex, increasing fusion promotion by HN as well as generally decreasing neuraminidase activity and increasing HN-receptor engagement. These results show that viruses may evolve rapidly in culture even during primary isolation of the virus and before the first passage and reveal features of fitness for humans that are obscured by rapid adaptation to laboratory conditions.Sho IketaniRyan C. SheanMarion FerrenNegar MakhsousDolly B. AquinoAmedee des GeorgesBert RimaCyrille MathieuMatteo PorottoAnne MosconaAlexander L. GreningerAmerican Society for Microbiologyarticleentry mechanismslung infectionmetagenomicsparainfluenza virusparamyxovirusviral evolutionMicrobiologyQR1-502ENmBio, Vol 9, Iss 4 (2018) |
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entry mechanisms lung infection metagenomics parainfluenza virus paramyxovirus viral evolution Microbiology QR1-502 |
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entry mechanisms lung infection metagenomics parainfluenza virus paramyxovirus viral evolution Microbiology QR1-502 Sho Iketani Ryan C. Shean Marion Ferren Negar Makhsous Dolly B. Aquino Amedee des Georges Bert Rima Cyrille Mathieu Matteo Porotto Anne Moscona Alexander L. Greninger Viral Entry Properties Required for Fitness in Humans Are Lost through Rapid Genomic Change during Viral Isolation |
description |
IMPORTANCE Human parainfluenza virus 3 is an important cause of morbidity and mortality among infants, the immunocompromised, and the elderly. Using deep genomic sequencing of HPIV-3-positive clinical material and its subsequent viral isolate, we discover a number of known and novel coding mutations in the main HPIV-3 attachment protein HN during brief exposure to immortalized cells. These mutations significantly alter function of the fusion complex, increasing fusion promotion by HN as well as generally decreasing neuraminidase activity and increasing HN-receptor engagement. These results show that viruses may evolve rapidly in culture even during primary isolation of the virus and before the first passage and reveal features of fitness for humans that are obscured by rapid adaptation to laboratory conditions. |
format |
article |
author |
Sho Iketani Ryan C. Shean Marion Ferren Negar Makhsous Dolly B. Aquino Amedee des Georges Bert Rima Cyrille Mathieu Matteo Porotto Anne Moscona Alexander L. Greninger |
author_facet |
Sho Iketani Ryan C. Shean Marion Ferren Negar Makhsous Dolly B. Aquino Amedee des Georges Bert Rima Cyrille Mathieu Matteo Porotto Anne Moscona Alexander L. Greninger |
author_sort |
Sho Iketani |
title |
Viral Entry Properties Required for Fitness in Humans Are Lost through Rapid Genomic Change during Viral Isolation |
title_short |
Viral Entry Properties Required for Fitness in Humans Are Lost through Rapid Genomic Change during Viral Isolation |
title_full |
Viral Entry Properties Required for Fitness in Humans Are Lost through Rapid Genomic Change during Viral Isolation |
title_fullStr |
Viral Entry Properties Required for Fitness in Humans Are Lost through Rapid Genomic Change during Viral Isolation |
title_full_unstemmed |
Viral Entry Properties Required for Fitness in Humans Are Lost through Rapid Genomic Change during Viral Isolation |
title_sort |
viral entry properties required for fitness in humans are lost through rapid genomic change during viral isolation |
publisher |
American Society for Microbiology |
publishDate |
2018 |
url |
https://doaj.org/article/116787510a404c218ec29e3d5ebc31b9 |
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