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Diversity and Complexity of Internally Deleted Viral Genomes in Influenza A Virus Subpopulations with Enhanced Interferon-Inducing Phenotypes

Influenza A virus (IAV) populations harbor large subpopulations of defective-interfering particles characterized by internally deleted viral genomes. These internally deleted genomes have demonstrated the ability to suppress infectivity and boost innate immunity, rendering them promising for therape...

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Autores principales: Ghorbani, Amir, Ngunjiri, John M., Rendon, Gloria, Brooke, Christopher B., Kenney, Scott P., Lee, Chang-Won
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10612045/
https://www.ncbi.nlm.nih.gov/pubmed/37896883
http://dx.doi.org/10.3390/v15102107
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author Ghorbani, Amir
Ngunjiri, John M.
Rendon, Gloria
Brooke, Christopher B.
Kenney, Scott P.
Lee, Chang-Won
author_facet Ghorbani, Amir
Ngunjiri, John M.
Rendon, Gloria
Brooke, Christopher B.
Kenney, Scott P.
Lee, Chang-Won
author_sort Ghorbani, Amir
collection PubMed
description Influenza A virus (IAV) populations harbor large subpopulations of defective-interfering particles characterized by internally deleted viral genomes. These internally deleted genomes have demonstrated the ability to suppress infectivity and boost innate immunity, rendering them promising for therapeutic and immunogenic applications. In this study, we aimed to investigate the diversity and complexity of the internally deleted IAV genomes within a panel of plaque-purified avian influenza viruses selected for their enhanced interferon-inducing phenotypes. Our findings unveiled that the abundance and diversity of internally deleted viral genomes were contingent upon the viral subculture and plaque purification processes. We observed a heightened occurrence of internally deleted genomes with distinct junctions in viral clones exhibiting enhanced interferon-inducing phenotypes, accompanied by additional truncation in the nonstructural 1 protein linker region (NS1Δ76-86). Computational analyses suggest the internally deleted IAV genomes can encode a broad range of carboxy-terminally truncated and intrinsically disordered proteins with variable lengths and amino acid composition. Further research is imperative to unravel the underlying mechanisms driving the increased diversity of internal deletions within the genomes of viral clones exhibiting enhanced interferon-inducing capacities and to explore their potential for modulating cellular processes and immunity.
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spelling pubmed-106120452023-10-29 Diversity and Complexity of Internally Deleted Viral Genomes in Influenza A Virus Subpopulations with Enhanced Interferon-Inducing Phenotypes Ghorbani, Amir Ngunjiri, John M. Rendon, Gloria Brooke, Christopher B. Kenney, Scott P. Lee, Chang-Won Viruses Article Influenza A virus (IAV) populations harbor large subpopulations of defective-interfering particles characterized by internally deleted viral genomes. These internally deleted genomes have demonstrated the ability to suppress infectivity and boost innate immunity, rendering them promising for therapeutic and immunogenic applications. In this study, we aimed to investigate the diversity and complexity of the internally deleted IAV genomes within a panel of plaque-purified avian influenza viruses selected for their enhanced interferon-inducing phenotypes. Our findings unveiled that the abundance and diversity of internally deleted viral genomes were contingent upon the viral subculture and plaque purification processes. We observed a heightened occurrence of internally deleted genomes with distinct junctions in viral clones exhibiting enhanced interferon-inducing phenotypes, accompanied by additional truncation in the nonstructural 1 protein linker region (NS1Δ76-86). Computational analyses suggest the internally deleted IAV genomes can encode a broad range of carboxy-terminally truncated and intrinsically disordered proteins with variable lengths and amino acid composition. Further research is imperative to unravel the underlying mechanisms driving the increased diversity of internal deletions within the genomes of viral clones exhibiting enhanced interferon-inducing capacities and to explore their potential for modulating cellular processes and immunity. MDPI 2023-10-17 /pmc/articles/PMC10612045/ /pubmed/37896883 http://dx.doi.org/10.3390/v15102107 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ghorbani, Amir
Ngunjiri, John M.
Rendon, Gloria
Brooke, Christopher B.
Kenney, Scott P.
Lee, Chang-Won
Diversity and Complexity of Internally Deleted Viral Genomes in Influenza A Virus Subpopulations with Enhanced Interferon-Inducing Phenotypes
title Diversity and Complexity of Internally Deleted Viral Genomes in Influenza A Virus Subpopulations with Enhanced Interferon-Inducing Phenotypes
title_full Diversity and Complexity of Internally Deleted Viral Genomes in Influenza A Virus Subpopulations with Enhanced Interferon-Inducing Phenotypes
title_fullStr Diversity and Complexity of Internally Deleted Viral Genomes in Influenza A Virus Subpopulations with Enhanced Interferon-Inducing Phenotypes
title_full_unstemmed Diversity and Complexity of Internally Deleted Viral Genomes in Influenza A Virus Subpopulations with Enhanced Interferon-Inducing Phenotypes
title_short Diversity and Complexity of Internally Deleted Viral Genomes in Influenza A Virus Subpopulations with Enhanced Interferon-Inducing Phenotypes
title_sort diversity and complexity of internally deleted viral genomes in influenza a virus subpopulations with enhanced interferon-inducing phenotypes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10612045/
https://www.ncbi.nlm.nih.gov/pubmed/37896883
http://dx.doi.org/10.3390/v15102107
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