Flu on the Fly


     
Flu on the Fly Autumn, when leaves, pumpkin spice, and flu are in the air, is a time to evaluate animal models of influenza pathogenesis and developments in flu research and treatment. This is an introductory reference for influenza studies with a few tips and tricks for utilizing mouse models.

Basics of Influenza

Influenza has three major subtypes: A, B and C.

  • Type A causes pandemic flu. It is further divided into subtypes, such as H1N1, where "H" stands for the hemagglutinin protein and "N" for the neurominidase protein.
  • Type B is seasonal flu, which is grouped into the Victoria and Yamagata lineages.
  • Type C causes a much milder disease.
More details can be found at the World Health Organization. Most flu research centers on development of vaccines and therapeutics for subtypes A & B.

According to the World Health Organization Fact sheet:

  • Seasonal influenza is an acute viral infection that spreads easily from person to person, circulates worldwide, and can affect people in any age group.
  • Seasonal influenza is a serious public health concern that causes severe illness and death in high risk populations.
  • Influenza vaccination is the most effective way to prevent disease.
  • Antiviral drugs are available for treatment, though influenza viruses can develop resistance to the drugs.
The National Institute of Health reports that global influenza pandemics occurred three times in the twentieth century alone: 1968, 1957, and 1918. The "Spanish Flu" of 1918-1919 caused more than 500,000 deaths in the United States and 50 million deaths worldwide.
Flu on the Fly
Source: https://www.cdc.gov/flu/about/disease/burden.htm


According to the Centers for Disease Control and Prevention (CDC), between five to twenty percent of the population in the US gets the flu each year, which costs an estimated $10.4 billion in direct health costs and has a total economic impact of over $87 billion.

Animal Models of Influenza

Modeling human disease in animal models can be challenging . Mice, rats, hamsters, guinea pigs, ferrets, and non-human primates are the most frequently used models for influenza research. Ferrets are considered to most accurately represent human influenza. Mouse models, many of which require disease adaptations to study influenza, are also commonly used; they are readily-available, well-characterized, and more affordable than other species1,2.

The focus of this article will be selection of appropriate mouse models rather than choice of species.

Some excellent primers on model selection for influenza can be found in Viral Pathogenesis, "Chapter 10 - Animal Models: No Model Is Perfect, but Many Are Useful3", Animal models for the study of influenza pathogenesis and therapy4, and Animal Models for Influenza Viruses: Implications for Universal Vaccine Development5.

Taconic Model Pages Related Taconic Biosciences' Model pages

Vaccine Development, Pathogenesis, and Therapeutics

  • Influenza viruses need adaptation via passaging to be accepted by most mouse models, and symptoms will differ in mice than in humans.
  • Aerosol and intranasal inoculation are typically utilized.
  • Typically weight loss, mortality, and lung pathology are used to measure response to the virus, as mice do not generally display sneezing or fever in response to influenza.
  • Studies of aged outbred mice are useful for studies of influenza complications, as they more appropriately mimic a human population and respond differently to the virus and therapeutics.
  • Humanized mouse models better mimic human disease responses than traditional inbred models, which typically measure weight loss to indicate response to disease.
  • Inbred mice are helpful in studying influenza therapeutics and vaccines. Identical genetic backgrounds enable consistent therapeutic responses across the population.
    • Traditionally, BALB/c and C57BL/6 mice are used however, some studies indicate the DBA/2 strain is useful for modeling influenza A & B without adaptation6,7.
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References:
1. Matsuoka Y, Lamirande EW, Subbarao K. The mouse model for influenza. Curr Protoc Microbiol. 2009 May; Chapter 15:Unit 15G.3. doi: 1 10.1002/9780471729259.mc15g03s13.
2. Mcdonald, RS., Sambol, AR., Heimbuch, et al (2012). Proportional mouse model for aerosol infection by influenza. Journal of Applied Microbiology, 113(4), 767-778. DOI: 10.1111/j.1365-2672.2012.05402.x.
3. Baxter, V. K., & Griffin, D. E. (2016). Animal Models: No Model is Perfect, But Many Are Useful. In Viral Pathogenesis: From Basics to Systems Biology: Third Edition pp. 125-138. Elsevier Inc.. DOI: 10.1016/B978-0-12-800964-2.00010-0.
4. Margine I & Krammer F. (2014)( Animal Models for Influenza Viruses: Implications for Universal Vaccine Development. Pathogens. 3(4), 845-874. doi: 10.3390/pathogens3040845.
5. Bouvier NM & Lowen AC. (2010) Animal Models for Influenza Virus Pathogenesis and Transmission Viruses. 2(8): 1530-1563. doi: 10.3390/v20801530.
6. Pica, N; Iyer, A; Ramos, I; Bouvier, NM; et. al (2011) The dba.2 mouse is susceptible to disease following infection with a broad, but limited, range of influenza a and b viruses. J. Virol. 85, 12825-12829.
7. Bouvier NM & Lowen AC. (2010) Animal Models for Influenza Virus Pathogenesis and Transmission Viruses. 2(8): 1530-1563. doi: 10.3390/v20801530.

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