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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Autores principales: 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
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Publicado: American Society for Microbiology 2018
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Acceso en línea:https://doaj.org/article/116787510a404c218ec29e3d5ebc31b9
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic entry mechanisms
lung infection
metagenomics
parainfluenza virus
paramyxovirus
viral evolution
Microbiology
QR1-502
spellingShingle 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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