Influenza A, SUbtype H1n1
This post is intended to be an overview, but much more detailed information can be found from the links at the bottom of this page. Please feel free to leave a question or comment!
Influenza, or the flu, is a common and highly contagious viral infection. While severity of infection varies year-to-year, the CDC estimates that there are between 9 million and 45 million cases of influenza in the United States alone each year, leading to 12,000-61,000 deaths. Globally, the WHO estimates there are roughly 1 billion cases annually.
Reports of influenza-like illness date back to 410 B.C. The most notable historic influenza, though, is that of 1918 – an H1N1 influenza virus which killed roughly 50 million people – approximately 3% of the world population at the time, and greater than the death toll of the First World War.
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Symptoms of mild influenza infection include:
- Sore throat
Influenza infection can become much more serious in individuals with pre-existing health conditions or weakened immune systems. One of the most common complications of influenza infection is pneumonia, which can lead to acute respiratory distress, and often results in hospitalization.
What exactly is the flu?
Viruses are submicroscopic pathogens composed of genetic material and a protein/lipid coat. Our genetic material is made up of DNA, or deoxyribonucleic acid, but the influenza virus carries something slightly different, called RNA (ribonucleic acid). These structures serve the same purpose of encoding the information to build necessary proteins. However, unlike our cells, viruses don’t have the cellular machinery needed to build those proteins. Instead, they must infect a host cell and recruit its machinery to synthesize new copies.
There are three types of influenza viruses which infect humans – A, B, and C – but influenza A is the most common. Influenza A viruses can be further classified into subtypes based on the proteins found on their surface, hemagglutinin (HA) and neuraminidase (NA), which are what the H#N# nomenclature refers to. For example, the 2009 influenza pandemic was Influenza type A, subtype H1N1, meaning that it had type 1 hemagglutinin and neuraminidase surface proteins.
The virus gains access to the host cell, typically in the respiratory tract, with the hemagglutinin surface protein, which binds a chemical structure embedded in the host cell membrane called sialic acid. This binding allows the virus to enter the cell and release its RNA segments inside, which are transported to the nucleus for processing. RNA acts like a code that provides the cell with instructions for building proteins, but the RNA carried by the influenza virus is negative-sense. This means that it must be converted to the complementary positive-sense RNA (now called messenger RNA or mRNA) before the cell can interpret it. This conversion is facilitated by an RNA polymerase enzyme. The original, negative-sense RNA is also copied to become the genetic material of the newly synthesized viruses.
mRNA leaves the nucleus, and organelles called ribosomes convert it into functional proteins. These proteins are combined with the copies of the original RNA material to form new virus particles, which fuse with the cell membrane to exit the cell. The virus is released when the neuraminidase surface protein clips its linkage to a sialic acid on the host cell surface, and the freed virus can go on to infect other host cells.
This process takes a toll on the host cell, as the majority of resources are put towards viral production. Additionally, presence of the virus in the cell activates the immune system, preparing the body to fight the infection. Intracellular immune proteins recognize various unique viral components, such as its RNA, and produce signaling molecules, such as interferons and interleukins, designed to restrict viral replication. The effects of this signaling protect the body, but also lead to many of the symptoms typically associated with influenza, such as fever, inflammation, and irritation of the respiratory tract.
Treatment and Prevention
While there are vaccines and antiviral treatments available, one of the most pharmacologically challenging characteristics of the influenza virus is its prominent ability to accrue mutations and recombine. Mutations occur frequently, and the segmented RNA can recombine if two different influenza subtypes infect the same cell.
These events make it difficult to create effective vaccines because the antibodies an individual makes against a strain in the vaccine may not be effective if they are exposed to a mutated or recombinant strain later on, which is why the influenza vaccine is recommended annually. Despite this challenge, vaccination is still the best way to prevent and lessen the severity of influenza infection. These issues have prompted prominent interest in the possibility of a universal influenza vaccine, which would theoretically target a well conserved portion of the virus, though, this project has proven difficult. As the research progresses, though, this will hopefully become a reality in the future.
You can learn more by exploring my Capstone Project Pages:
- Clinical Characterization
- Identification and Characterization of the Infectious Agent
- Cellular & Molecular Basis of Infection
- Host Immunity & Preserving the Healthy State
- Treatment, Prevention, & Transmission
- Examining Genetic Factors & Predispositions
Or, click below to view my Capstone Project Landing Page.
- CDC. Disease Burden of Influenza. (Accessed April 21, 2020) https://www.cdc.gov/flu/about/burden/index.html
- WHO. Global Influenza Strategy 2019-2030. (Accessed April 21, 2020) https://www.who.int/influenza/Global_Influenza_Strategy_2019_2030_Summary_English.pdf?ua=1
- History. Influenza. 2020 (Accessed April 22, 2020). https://www.history.com/topics/inventions/flu
- CDC. Types of Influenza Viruses. (Accessed March 12, 2020) https://www.cdc.gov/flu/about/viruses/types.html
- Eisenstein, M. Towards a universal flu vaccine. Nature Outlook. 2019 https://www.nature.com/articles/d41586-019-02751-w
- Chen, X.; Liu, S.; Goraya, M.U.; Maarouf, M.; Huang, S.; and Chen, J. Host Immune Response to Influenza A Virus Infection. Front Immunol. 2018, 9: 320. https://dx.doi.org/10.3389%2Ffimmu.2018.00320
- Krammer, F.; Smith, G. J. D.; Fouchier, R. A. M.; Peiris, M.; Kedzierska, K.; Doherty, P. C.; Palese, P.; Shaw, M. L.; Treanor, J.; Webster, R. G.; et al. Influenza. Nat. Rev. Dis. Primer 2018, 4 (1), 1–21. https://doi.org/10.1038/s41572-018-0002-y
- Dou, D.; Revol, R.; Ostbye, H.; Wang, H.; and Daniels, R. Influenza A Virus Cell Entry, Replication, Virion Assembly and Movement. Front Immunol. 2018, 9: 1581. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062596
Note: Images in main text are not linked to direct sources because they are original content.
Timeline & Timeline Images
- CDC. Influenza (Flu) (Accessed Apr 14, 2020) https://www.cdc.gov/flu/
- CDC. 1918 Commemoration Historical Images [Image] (Accessed Apr 21, 2020). https://www.cdc.gov/flu/pandemic-resources/1918-commemoration/historical-images.htm#
- Wikipedia. Richard Pfeiffer [Image] (Accessed Apr 21, 2020). https://en.wikipedia.org/wiki/Richard_Friedrich_Johannes_Pfeiffer
- Machemer, T. How a few sick tobacco plants led scientists to unravel the truth about viruses. Smithsonian, 2020. (Accessed Apr 21, 2020). https://www.smithsonianmag.com/science-nature/what-are-viruses-history-tobacco-mosaic-disease-180974480/
- Huston History: The flu pandemic Huston faced 100 years ago [Image] (Accessed Apr 21, 2020). https://www.google.com/url?sa=i&url=https%3A%2F%2Fwww.click2houston.com%2Fhouston-life%2F2020%2F03%2F24%2Fhouston-history-the-flu-pandemic-houston-faced-100-years-ago%2F&psig=AOvVaw1PSbrMWpqo90qUfsjplXiJ&ust=1587691892211000&source=images&cd=vfe&ved=0CA0QjhxqFwoTCNC0rrSz_egCFQAAAAAdAAAAABAD
- Science Photo. Influenza A Virus, TEM [Image]. (Accessed Apr 21, 2020). https://www.google.com/url?sa=i&url=https%3A%2F%2Fwww.sciencephoto.com%2Fmedia%2F864731%2Fview%2Finfluenza-a-virus-tem&psig=AOvVaw04ffg2O0AbH9Fg2K9ISnAA&ust=1587692564403000&source=images&cd=vfe&ved=0CAIQjRxqFwoTCID79e61_egCFQAAAAAdAAAAABAD
- Virology Blog. The neuraminidase of the influenza virus [Image]. 2013. (Accessed Apr 21, 2020). https://www.virology.ws/2013/11/05/the-neuraminidase-of-influenza-virus/
- Drugs.com. Amantadine Syrup [Image] (Accessed Apr 21, 2020). https://www.drugs.com/pro/amantadine-syrup.html
- Tao, Y.J.; and Zheng, W. Visualizing the Influenza Genome (Figure 1) [Image]. Science. 2012, 338(6114): 1545-1546. https://science-sciencemag-org.muhlenberg.idm.oclc.org/content/338/6114/1545
- Moisse, K. Young Swine Flu Survivor Gets Kidney from Mom. ABC News. 2013 (Accessed Apr 21, 2020). https://abcnews.go.com/Health/young-swine-flu-survivor-kidney-mom/story?id=19826287