Animal Models for Influenza A Virus Infection Incorporating the Involvement of Innate Host Defenses: Enhanced Translational Value of the Porcine Model

Sofie Maiken Riisgård Starbæk*, Louise Brogaard, Harry D Dawson, Allen D Smith, Peter M. H. Heegaard, Lars E. Larsen, Gregers Jungersen, Kerstin Skovgaard

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Influenza is a viral respiratory disease having a major impact on public health. Influenza A virus (IAV) usually causes mild transitory disease in humans. However, in specific groups of individuals such as severely obese, the elderly, and individuals with underlying inflammatory conditions, IAV can cause severe illness or death. In this review, relevant small and large animal models for human IAV infection, including the pig, ferret, and mouse, are discussed. The focus is on the pig as a large animal model for human IAV infection as well as on the associated innate immune response. Pigs are natural hosts for the same IAV subtypes as humans, they develop clinical disease mirroring human symptoms, they have similar lung anatomy, and their respiratory physiology and immune responses to IAV infection are remarkably similar to what is observed in humans. The pig model shows high face and target validity for human IAV infection, making it suitable for modeling many aspects of influenza, including increased risk of severe disease and impaired vaccine response due to underlying pathologies such as low-grade inflammation. Comparative analysis of proteins involved in viral pattern recognition, interferon responses, and regulation of interferon-stimulated genes reveals a significantly higher degree of similarity between pig, ferret, and human compared with mice. It is concluded that the pig is a promising animal model displaying substantial human translational value with the ability to provide essential insights into IAV infection, pathogenesis, and immunity
Original languageEnglish
Article numberily009
JournalI L A R Journal
Volume59
Issue number3
Pages (from-to)323-337
Number of pages15
ISSN1084-2020
DOIs
Publication statusPublished - 2018

Keywords

  • Animal model
  • Antiviral
  • Inflammation A virus
  • Innate immune response
  • MicroRNA
  • Translational value
  • Validity

Cite this

@article{74d085eccf95499da4ee1df9d1c4d472,
title = "Animal Models for Influenza A Virus Infection Incorporating the Involvement of Innate Host Defenses: Enhanced Translational Value of the Porcine Model",
abstract = "Influenza is a viral respiratory disease having a major impact on public health. Influenza A virus (IAV) usually causes mild transitory disease in humans. However, in specific groups of individuals such as severely obese, the elderly, and individuals with underlying inflammatory conditions, IAV can cause severe illness or death. In this review, relevant small and large animal models for human IAV infection, including the pig, ferret, and mouse, are discussed. The focus is on the pig as a large animal model for human IAV infection as well as on the associated innate immune response. Pigs are natural hosts for the same IAV subtypes as humans, they develop clinical disease mirroring human symptoms, they have similar lung anatomy, and their respiratory physiology and immune responses to IAV infection are remarkably similar to what is observed in humans. The pig model shows high face and target validity for human IAV infection, making it suitable for modeling many aspects of influenza, including increased risk of severe disease and impaired vaccine response due to underlying pathologies such as low-grade inflammation. Comparative analysis of proteins involved in viral pattern recognition, interferon responses, and regulation of interferon-stimulated genes reveals a significantly higher degree of similarity between pig, ferret, and human compared with mice. It is concluded that the pig is a promising animal model displaying substantial human translational value with the ability to provide essential insights into IAV infection, pathogenesis, and immunity",
keywords = "Animal model, Antiviral, Inflammation A virus, Innate immune response, MicroRNA, Translational value, Validity",
author = "Starb{\ae}k, {Sofie Maiken Riisg{\aa}rd} and Louise Brogaard and Dawson, {Harry D} and Smith, {Allen D} and Heegaard, {Peter M. H.} and Larsen, {Lars E.} and Gregers Jungersen and Kerstin Skovgaard",
year = "2018",
doi = "10.1093/ilar/ily009",
language = "English",
volume = "59",
pages = "323--337",
journal = "I L A R Journal",
issn = "1084-2020",
publisher = "Oxford University Press",
number = "3",

}

Animal Models for Influenza A Virus Infection Incorporating the Involvement of Innate Host Defenses: Enhanced Translational Value of the Porcine Model. / Starbæk, Sofie Maiken Riisgård; Brogaard, Louise; Dawson, Harry D; Smith, Allen D; Heegaard, Peter M. H.; Larsen, Lars E.; Jungersen, Gregers; Skovgaard, Kerstin.

In: I L A R Journal, Vol. 59, No. 3, ily009, 2018, p. 323-337.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Animal Models for Influenza A Virus Infection Incorporating the Involvement of Innate Host Defenses: Enhanced Translational Value of the Porcine Model

AU - Starbæk, Sofie Maiken Riisgård

AU - Brogaard, Louise

AU - Dawson, Harry D

AU - Smith, Allen D

AU - Heegaard, Peter M. H.

AU - Larsen, Lars E.

AU - Jungersen, Gregers

AU - Skovgaard, Kerstin

PY - 2018

Y1 - 2018

N2 - Influenza is a viral respiratory disease having a major impact on public health. Influenza A virus (IAV) usually causes mild transitory disease in humans. However, in specific groups of individuals such as severely obese, the elderly, and individuals with underlying inflammatory conditions, IAV can cause severe illness or death. In this review, relevant small and large animal models for human IAV infection, including the pig, ferret, and mouse, are discussed. The focus is on the pig as a large animal model for human IAV infection as well as on the associated innate immune response. Pigs are natural hosts for the same IAV subtypes as humans, they develop clinical disease mirroring human symptoms, they have similar lung anatomy, and their respiratory physiology and immune responses to IAV infection are remarkably similar to what is observed in humans. The pig model shows high face and target validity for human IAV infection, making it suitable for modeling many aspects of influenza, including increased risk of severe disease and impaired vaccine response due to underlying pathologies such as low-grade inflammation. Comparative analysis of proteins involved in viral pattern recognition, interferon responses, and regulation of interferon-stimulated genes reveals a significantly higher degree of similarity between pig, ferret, and human compared with mice. It is concluded that the pig is a promising animal model displaying substantial human translational value with the ability to provide essential insights into IAV infection, pathogenesis, and immunity

AB - Influenza is a viral respiratory disease having a major impact on public health. Influenza A virus (IAV) usually causes mild transitory disease in humans. However, in specific groups of individuals such as severely obese, the elderly, and individuals with underlying inflammatory conditions, IAV can cause severe illness or death. In this review, relevant small and large animal models for human IAV infection, including the pig, ferret, and mouse, are discussed. The focus is on the pig as a large animal model for human IAV infection as well as on the associated innate immune response. Pigs are natural hosts for the same IAV subtypes as humans, they develop clinical disease mirroring human symptoms, they have similar lung anatomy, and their respiratory physiology and immune responses to IAV infection are remarkably similar to what is observed in humans. The pig model shows high face and target validity for human IAV infection, making it suitable for modeling many aspects of influenza, including increased risk of severe disease and impaired vaccine response due to underlying pathologies such as low-grade inflammation. Comparative analysis of proteins involved in viral pattern recognition, interferon responses, and regulation of interferon-stimulated genes reveals a significantly higher degree of similarity between pig, ferret, and human compared with mice. It is concluded that the pig is a promising animal model displaying substantial human translational value with the ability to provide essential insights into IAV infection, pathogenesis, and immunity

KW - Animal model

KW - Antiviral

KW - Inflammation A virus

KW - Innate immune response

KW - MicroRNA

KW - Translational value

KW - Validity

U2 - 10.1093/ilar/ily009

DO - 10.1093/ilar/ily009

M3 - Journal article

VL - 59

SP - 323

EP - 337

JO - I L A R Journal

JF - I L A R Journal

SN - 1084-2020

IS - 3

M1 - ily009

ER -