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

Amir Ghorbani; John M Ngunjiri; Gloria Rendon; Christopher B Brooke; Scott P Kenney; Chang-Won Lee

doi:10.3390/v15102107

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

Viruses. 2023 Oct 17;15(10):2107. doi: 10.3390/v15102107.

Authors

Amir Ghorbani^{1

2}, John M Ngunjiri², Gloria Rendon³, Christopher B Brooke^{3

4}, Scott P Kenney^{1

2}, Chang-Won Lee⁵

Affiliations

¹ Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
² Center for Food Animal Health, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH 44691, USA.
³ Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
⁴ Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
⁵ Southeast Poultry Research Laboratory, US National Poultry Research Center, USDA, ARS, Athens, GA 30605, USA.

Abstract

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.

Keywords: NS1 truncation; defective genomes; influenza; interferon; subpopulations.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Genome, Viral
Humans
Immunity, Innate
Influenza A virus*
Influenza, Human*
Interferons / genetics
RNA, Viral / genetics
Viral Nonstructural Proteins / metabolism
Virus Replication / genetics

Substances

Interferons
RNA, Viral
Viral Nonstructural Proteins

Grants and funding

This work was partly supported by The Ohio State University, Ohio Agricultural Research and Development Center and U.S. Department of Agriculture, ARS CRIS Project 6040-32000-081-000D.