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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Main Authors: 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
Format: Article
Language:English
Published: American Society for Microbiology 2018-09-01
Series:mBio
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/mBio.00898-18
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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
collection DOAJ
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.
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spelling doaj.art-116787510a404c218ec29e3d5ebc31b92022-12-21T18:02:01ZengAmerican Society for MicrobiologymBio2150-75112018-09-019410.1128/mBio.00898-18Viral Entry Properties Required for Fitness in Humans Are Lost through Rapid Genomic Change during Viral IsolationSho Iketani0Ryan C. Shean1Marion Ferren2Negar Makhsous3Dolly B. Aquino4Amedee des Georges5Bert Rima6Cyrille Mathieu7Matteo Porotto8Anne Moscona9Alexander L. Greninger10Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, USADepartment of Laboratory Medicine, University of Washington, Seattle, Washington, USACenter for Host-Pathogen Interaction, Columbia University Medical Center, New York, New York, USADepartment of Laboratory Medicine, University of Washington, Seattle, Washington, USADepartment of Laboratory Medicine, University of Washington, Seattle, Washington, USADepartment of Chemistry and Biochemistry, Advanced Science Research Center, City College of New York, New York, New York, USACenter for Experimental Medicine, Queens University, Belfast, Northern Ireland, United KingdomCenter for Host-Pathogen Interaction, Columbia University Medical Center, New York, New York, USACenter for Host-Pathogen Interaction, Columbia University Medical Center, New York, New York, USADepartment of Microbiology and Immunology, Columbia University Medical Center, New York, New York, USADepartment of Laboratory Medicine, University of Washington, Seattle, Washington, USAIMPORTANCE 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.https://journals.asm.org/doi/10.1128/mBio.00898-18entry mechanismslung infectionmetagenomicsparainfluenza virusparamyxovirusviral evolution
spellingShingle 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
mBio
entry mechanisms
lung infection
metagenomics
parainfluenza virus
paramyxovirus
viral evolution
title 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_short 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
topic entry mechanisms
lung infection
metagenomics
parainfluenza virus
paramyxovirus
viral evolution
url https://journals.asm.org/doi/10.1128/mBio.00898-18
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