Combined Proteomics/Genomics Approach Reveals Proteomic Changes of Mature Virions as a Novel Poxvirus Adaptation Mechanism

DNA viruses, like poxviruses, possess a highly stable genome, suggesting that adaptation of virus particles to specific cell types is not restricted to genomic changes. Cowpox viruses are zoonotic poxviruses with an extraordinarily broad host range, demonstrating their adaptive potential in vivo. To...

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Main Authors: Marica Grossegesse, Joerg Doellinger, Alona Tyshaieva, Lars Schaade, Andreas Nitsche
Format: Article
Language:English
Published: MDPI AG 2017-11-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/9/11/337
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author Marica Grossegesse
Joerg Doellinger
Alona Tyshaieva
Lars Schaade
Andreas Nitsche
author_facet Marica Grossegesse
Joerg Doellinger
Alona Tyshaieva
Lars Schaade
Andreas Nitsche
author_sort Marica Grossegesse
collection DOAJ
description DNA viruses, like poxviruses, possess a highly stable genome, suggesting that adaptation of virus particles to specific cell types is not restricted to genomic changes. Cowpox viruses are zoonotic poxviruses with an extraordinarily broad host range, demonstrating their adaptive potential in vivo. To elucidate adaptation mechanisms of poxviruses, we isolated cowpox virus particles from a rat and passaged them five times in a human and a rat cell line. Subsequently, we analyzed the proteome and genome of the non-passaged virions and each passage. While the overall viral genome sequence was stable during passaging, proteomics revealed multiple changes in the virion composition. Interestingly, an increased viral fitness in human cells was observed in the presence of increased immunomodulatory protein amounts. As the only minor variant with increasing frequency during passaging was located in a viral RNA polymerase subunit and, moreover, most minor variants were found in transcription-associated genes, protein amounts were presumably regulated at transcription level. This study is the first comparative proteome analysis of virus particles before and after cell culture propagation, revealing proteomic changes as a novel poxvirus adaptation mechanism.
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spelling doaj.art-c52eec2840884af59a5ccd5abf898fd02022-12-22T03:35:19ZengMDPI AGViruses1999-49152017-11-0191133710.3390/v9110337v9110337Combined Proteomics/Genomics Approach Reveals Proteomic Changes of Mature Virions as a Novel Poxvirus Adaptation MechanismMarica Grossegesse0Joerg Doellinger1Alona Tyshaieva2Lars Schaade3Andreas Nitsche4Centre for Biological Threats and Special Pathogens, Highly Pathogenic Viruses (ZBS 1), Robert Koch Institute, Seestr. 10, 13353 Berlin, GermanyCentre for Biological Threats and Special Pathogens, Highly Pathogenic Viruses (ZBS 1), Robert Koch Institute, Seestr. 10, 13353 Berlin, GermanyCentre for Biological Threats and Special Pathogens, Highly Pathogenic Viruses (ZBS 1), Robert Koch Institute, Seestr. 10, 13353 Berlin, GermanyCentre for Biological Threats and Special Pathogens (ZBS), Robert Koch Institute, Nordufer 20, 13353 Berlin, GermanyCentre for Biological Threats and Special Pathogens, Highly Pathogenic Viruses (ZBS 1), Robert Koch Institute, Seestr. 10, 13353 Berlin, GermanyDNA viruses, like poxviruses, possess a highly stable genome, suggesting that adaptation of virus particles to specific cell types is not restricted to genomic changes. Cowpox viruses are zoonotic poxviruses with an extraordinarily broad host range, demonstrating their adaptive potential in vivo. To elucidate adaptation mechanisms of poxviruses, we isolated cowpox virus particles from a rat and passaged them five times in a human and a rat cell line. Subsequently, we analyzed the proteome and genome of the non-passaged virions and each passage. While the overall viral genome sequence was stable during passaging, proteomics revealed multiple changes in the virion composition. Interestingly, an increased viral fitness in human cells was observed in the presence of increased immunomodulatory protein amounts. As the only minor variant with increasing frequency during passaging was located in a viral RNA polymerase subunit and, moreover, most minor variants were found in transcription-associated genes, protein amounts were presumably regulated at transcription level. This study is the first comparative proteome analysis of virus particles before and after cell culture propagation, revealing proteomic changes as a novel poxvirus adaptation mechanism.https://www.mdpi.com/1999-4915/9/11/337poxvirusadaptationproteomicsgenomicscowpox viruscell culturepassaging
spellingShingle Marica Grossegesse
Joerg Doellinger
Alona Tyshaieva
Lars Schaade
Andreas Nitsche
Combined Proteomics/Genomics Approach Reveals Proteomic Changes of Mature Virions as a Novel Poxvirus Adaptation Mechanism
Viruses
poxvirus
adaptation
proteomics
genomics
cowpox virus
cell culture
passaging
title Combined Proteomics/Genomics Approach Reveals Proteomic Changes of Mature Virions as a Novel Poxvirus Adaptation Mechanism
title_full Combined Proteomics/Genomics Approach Reveals Proteomic Changes of Mature Virions as a Novel Poxvirus Adaptation Mechanism
title_fullStr Combined Proteomics/Genomics Approach Reveals Proteomic Changes of Mature Virions as a Novel Poxvirus Adaptation Mechanism
title_full_unstemmed Combined Proteomics/Genomics Approach Reveals Proteomic Changes of Mature Virions as a Novel Poxvirus Adaptation Mechanism
title_short Combined Proteomics/Genomics Approach Reveals Proteomic Changes of Mature Virions as a Novel Poxvirus Adaptation Mechanism
title_sort combined proteomics genomics approach reveals proteomic changes of mature virions as a novel poxvirus adaptation mechanism
topic poxvirus
adaptation
proteomics
genomics
cowpox virus
cell culture
passaging
url https://www.mdpi.com/1999-4915/9/11/337
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