Cross-Species Genome-Wide Analysis Reveals Molecular and Functional Diversity of the Unconventional Interferon-ω Subtype
Innate immune interferons (IFNs), particularly type I IFNs, are primary mediators regulating animal antiviral, antitumor, and cell-proliferative activity. These antiviral cytokines have evolved remarkable molecular and functional diversity to confront ever-evolving viral threats and physiological re...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-06-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01431/full |
| _version_ | 1819066924255936512 |
|---|---|
| author | Lauren E. Shields Jordan Jennings Qinfang Liu Jinhwa Lee Wenjun Ma Frank Blecha Laura C. Miller Yongming Sang |
| author_facet | Lauren E. Shields Jordan Jennings Qinfang Liu Jinhwa Lee Wenjun Ma Frank Blecha Laura C. Miller Yongming Sang |
| author_sort | Lauren E. Shields |
| collection | DOAJ |
| description | Innate immune interferons (IFNs), particularly type I IFNs, are primary mediators regulating animal antiviral, antitumor, and cell-proliferative activity. These antiviral cytokines have evolved remarkable molecular and functional diversity to confront ever-evolving viral threats and physiological regulation. We have annotated IFN gene families across 110 animal genomes, and showed that IFN genes, after originating in jawed fishes, had several significant evolutionary surges in vertebrate species of amphibians, bats and ungulates, particularly pigs and cattle. For example, pigs have the largest but still expanding type I IFN family consisting of nearly 60 IFN-coding genes that encode seven IFN subtypes including multigene subtypes of IFN-α, -δ, and -ω. Whereas, subtypes such as IFN-α and -β have been widely studied in many species, the unconventional subtypes such as IFN-ω have barely been investigated. We have cross-species defined the IFN evolution, and shown that unconventional IFN subtypes particularly the IFN-ω subtype have evolved several novel features including: (1) being a signature multi-gene subtype expanding primarily in mammals such as bats and ungulates, (2) emerging isoforms that have superior antiviral potency than typical IFN-α, (3) highly cross-species antiviral (but little anti-proliferative) activity exerted in cells of humans and other mammalian species, and (4) demonstrating potential novel molecular and functional properties. This study focused on IFN-ω to investigate the immunogenetic evolution and functional diversity of unconventional IFN subtypes, which may further IFN-based novel antiviral design pertinent to their cross-species high antiviral and novel activities. |
| first_indexed | 2024-12-21T16:10:05Z |
| format | Article |
| id | doaj.art-453d4dd3173745e49e478364f2a1c739 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T16:10:05Z |
| publishDate | 2019-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-453d4dd3173745e49e478364f2a1c7392022-12-21T18:57:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-06-011010.3389/fimmu.2019.01431459179Cross-Species Genome-Wide Analysis Reveals Molecular and Functional Diversity of the Unconventional Interferon-ω SubtypeLauren E. Shields0Jordan Jennings1Qinfang Liu2Jinhwa Lee3Wenjun Ma4Frank Blecha5Laura C. Miller6Yongming Sang7Department of Agricultural and Environmental Sciences, College of Agriculture, Tennessee State University, Nashville, TN, United StatesDepartment of Agricultural and Environmental Sciences, College of Agriculture, Tennessee State University, Nashville, TN, United StatesDepartment of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, United StatesDepartment of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, United StatesDepartment of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, United StatesDepartment of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, United StatesVirus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, United StatesDepartment of Agricultural and Environmental Sciences, College of Agriculture, Tennessee State University, Nashville, TN, United StatesInnate immune interferons (IFNs), particularly type I IFNs, are primary mediators regulating animal antiviral, antitumor, and cell-proliferative activity. These antiviral cytokines have evolved remarkable molecular and functional diversity to confront ever-evolving viral threats and physiological regulation. We have annotated IFN gene families across 110 animal genomes, and showed that IFN genes, after originating in jawed fishes, had several significant evolutionary surges in vertebrate species of amphibians, bats and ungulates, particularly pigs and cattle. For example, pigs have the largest but still expanding type I IFN family consisting of nearly 60 IFN-coding genes that encode seven IFN subtypes including multigene subtypes of IFN-α, -δ, and -ω. Whereas, subtypes such as IFN-α and -β have been widely studied in many species, the unconventional subtypes such as IFN-ω have barely been investigated. We have cross-species defined the IFN evolution, and shown that unconventional IFN subtypes particularly the IFN-ω subtype have evolved several novel features including: (1) being a signature multi-gene subtype expanding primarily in mammals such as bats and ungulates, (2) emerging isoforms that have superior antiviral potency than typical IFN-α, (3) highly cross-species antiviral (but little anti-proliferative) activity exerted in cells of humans and other mammalian species, and (4) demonstrating potential novel molecular and functional properties. This study focused on IFN-ω to investigate the immunogenetic evolution and functional diversity of unconventional IFN subtypes, which may further IFN-based novel antiviral design pertinent to their cross-species high antiviral and novel activities.https://www.frontiersin.org/article/10.3389/fimmu.2019.01431/fullinterferoninterferon-ω subtypeantiviralmolecular evolutioncytokine |
| spellingShingle | Lauren E. Shields Jordan Jennings Qinfang Liu Jinhwa Lee Wenjun Ma Frank Blecha Laura C. Miller Yongming Sang Cross-Species Genome-Wide Analysis Reveals Molecular and Functional Diversity of the Unconventional Interferon-ω Subtype Frontiers in Immunology interferon interferon-ω subtype antiviral molecular evolution cytokine |
| title | Cross-Species Genome-Wide Analysis Reveals Molecular and Functional Diversity of the Unconventional Interferon-ω Subtype |
| title_full | Cross-Species Genome-Wide Analysis Reveals Molecular and Functional Diversity of the Unconventional Interferon-ω Subtype |
| title_fullStr | Cross-Species Genome-Wide Analysis Reveals Molecular and Functional Diversity of the Unconventional Interferon-ω Subtype |
| title_full_unstemmed | Cross-Species Genome-Wide Analysis Reveals Molecular and Functional Diversity of the Unconventional Interferon-ω Subtype |
| title_short | Cross-Species Genome-Wide Analysis Reveals Molecular and Functional Diversity of the Unconventional Interferon-ω Subtype |
| title_sort | cross species genome wide analysis reveals molecular and functional diversity of the unconventional interferon ω subtype |
| topic | interferon interferon-ω subtype antiviral molecular evolution cytokine |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01431/full |
| work_keys_str_mv | AT laureneshields crossspeciesgenomewideanalysisrevealsmolecularandfunctionaldiversityoftheunconventionalinterferonōsubtype AT jordanjennings crossspeciesgenomewideanalysisrevealsmolecularandfunctionaldiversityoftheunconventionalinterferonōsubtype AT qinfangliu crossspeciesgenomewideanalysisrevealsmolecularandfunctionaldiversityoftheunconventionalinterferonōsubtype AT jinhwalee crossspeciesgenomewideanalysisrevealsmolecularandfunctionaldiversityoftheunconventionalinterferonōsubtype AT wenjunma crossspeciesgenomewideanalysisrevealsmolecularandfunctionaldiversityoftheunconventionalinterferonōsubtype AT frankblecha crossspeciesgenomewideanalysisrevealsmolecularandfunctionaldiversityoftheunconventionalinterferonōsubtype AT lauracmiller crossspeciesgenomewideanalysisrevealsmolecularandfunctionaldiversityoftheunconventionalinterferonōsubtype AT yongmingsang crossspeciesgenomewideanalysisrevealsmolecularandfunctionaldiversityoftheunconventionalinterferonōsubtype |