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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Format: | Article |
Language: | English |
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American Society for Microbiology
2018-09-01
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Series: | mBio |
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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. |
first_indexed | 2024-12-23T03:20:37Z |
format | Article |
id | doaj.art-116787510a404c218ec29e3d5ebc31b9 |
institution | Directory Open Access Journal |
issn | 2150-7511 |
language | English |
last_indexed | 2024-12-23T03:20:37Z |
publishDate | 2018-09-01 |
publisher | American Society for Microbiology |
record_format | Article |
series | mBio |
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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