Written by: Klara Martinovic

Edited by: Maria Ines Berrojo Romeyro Mascarenhas

In the scientific corner for this and next week, our topic will be the main character of this year’s project – Influenza A virus. The topic of this week is focused on the viral particle structure and the life cycle of the Influenza A virus. Next week you will find out more details about how different Influenza subtypes occur, how the occurrence of those subtypes affected the past, and how they will continue to condition the future.

Influenza A virus causes one of the most common respiratory diseases globally, seasonal flu or acute febrile respiratory tract infection, that occurs intermittently in both north and south hemispheres. It is mainly aerosol transmitted via coughing and sneezing, but also via fomites. It is most easily spread in the dry air of a cold climate. At the higher risk of developing a more severe disease are children, elderly, immunocompromised individuals, and pregnant women.

Influenza A together with Influenza B, C, and D is a part of the virus family Orthomyxoviridae; they all the share common characteristic of having segmented antisense (-) single-strand RNA genome. Influenza B is also a part of the annual epidemic flu, while Influenza C, even though it infects humans, does not cause any disease. Influenza D does not infect humans, only animals like pigs and cattle.

Viral particles have helical protein capsid which allows virion to change the structure from spherical to filamentous. It is enveloped with the phospholipid membrane from the host cell plasma membrane in which two viral envelope glycoproteins are inserted; hemagglutinin (HA) – attachment protein that binds to cell surface receptors, and neuraminidase (NA) – works as scissors involved in the detachment of the virus from the cell surface. Eight genome segments are wrapped with nucleocapsid proteins (NP) and RNA polymerase complex consisting of 3 proteins PA, PB1, and PB2 attached to the ends of RNA molecules.

It infects both upper and lower respiratory tracts, but mainly attaches to epithelial cells of the trachea and the bronchi. 

Hemagglutinin attaches specifically to α2-6 linked sialic acids receptors on the surface of the human epithelial cells. The virus is taken up by endocytosis and when the endosome fuses with the lysosome it becomes acidic, which induces membrane fusion and the release of ribonucleoprotein (RNP) core in the cytosol. Even though most of the RNA viruses replicate in the cytosol, Influenza virus is an exception and RNPs are transported into the nucleus where it replicates. In the nucleus, mRNAs for production of new viral proteins in the cytosol are transcribed from viral (-) ssRNA. Also, full-length genome copies of all 8 gene segments are replicated and will be packed into new virions once they reach the membrane.  Newly synthesized viral particles bud out from the cell surface coated in cell membrane with inserted HA and NA glycoproteins. Neuraminidase then cleaves off the sialic acid residues to release viral particles from the surface of the cell.  

Most of the symptoms of influenza infection are related to the host immune response to the virus and the most common ones are fever, sore throat, cough, fatigue, and muscle pain. The virus is recognized via Toll-like receptors on the cell surface and it triggers a strong interferon response which puts the cell into an anti-viral state in which the cell protein production is shut off. The combination of that response with the production of fever-causing inflammatory interleukins disables viral replication- that is the core purpose of the immune response which we experience as symptoms when we are infected with Influenza.

References:

  1. Herold, S., Becker, C., Ridge, K. and Budinger, G. Influenza virus-induced lung injury: pathogenesis and implications for treatment. European Respiratory Journal, 45(5), 1463-1478 (2015).
  2. Acheson, N. H. Influenza Viruses, Fundamentals of Molecular Virology, 210-224 (2011). Dalius J. Briedis.
  3. Flint, J., Racaniello, V. R., Rall, G. F. et al. Principles of Virology,4th edition, 392 (2015). ASM Press.

Note: this paper is largely based on a lecture given by professor Patrik Ellström at Uppsala University.

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