Influenza A

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Contents

Introduction

Influenza A is a highly contagious virus with the ability to cause pandemics, unlike influenza types B and C. It has a distinctive structure- it is spherical in shape, composed of an RNA and nucleoprotein core surrounded by a matrix protein, all contained in a lipid bilayer covered in hemagglutinin and neuraminidase spikes [1].

Causes of disease

The Influenza A virus causes a respiratory tract infection and can be contracted by airborne transmission from an infected person when they cough or sneeze. The virus can also be contracted by touching an object or surface that has been contaminated by the infected person, and then touching ones nose, mouth or eyes, as the virus can survive for a short while outside of the body [2].

The Influenza A virus infects cells via its two surface glycoproteins, hemagglutinin and neuraminidase. Hemagglutinin is required for attaching the virus to the host cell and is a membrane-bound trimer with three HA1 and three HA2 polypeptide chains containing binding pockets [3]. The HA1 binding pocket contains amino acid residues which allow hemagglutinin to recognise and bind to the sialic acid on surface of the host cell [4]. The viral membrane and cell membrane then fuse and the virus is ingested into the cell via receptor-mediated endocytosis [5]. When the virus is ingested into the cell this way the virus develops a double membrane as it is surrounded by a section from the membrane of the host cell. This is called a caspid coat [6]. Once inside the cell the virus is transported to an endosome, where the acid pH causes the hemagglutinin structure to alter and attach to lipid in the endosomal wall [7]. Hydrogen ions pass from the endosome through the M2 ion channel in the viral membrane, causing the virus to become uncoated and release its RNA genome into the cytosol of the cell [8]. The RNA can then replicate inside the cell, forming new virions [9]. The other cell surface glycoprotein, neuraminidase, is a membrane-bound tetramer and is required to separate the virus and the cell. Neuraminidase cleaves sialic acid so that hemagglutinin becomes unbound from the cell and the virus is released.

The Influenza A virus infects the respiratory cells in lungs and while the immune system may be capable of generating antibodies in response, the glycoproteins on the surface of the virus randomly mutate, undergoing antigenic drift or shift [10] [11][12]. This means that once the body has immunized itself and recovered from the first strain of the virus, the mutated version can then again cause infection as the antibodies to the first strain will not recognise the disease until infection has already spread [13]. During antigenic drift, mutations occur within the active sites of haemagglutinin or neuraminidase, causing the virus to become unrecognizable to the antibodies already present [14] [15]. Influenza A (H7N9) is normally found in birds but this virus is now able to infect humans and can be detected. The route of transmission is still uncertain and there is ongoing research to find if the virus can be passed from human to human.  [16]

Prevention of Disease

The random mutation of influenza virus makes it difficult to prevent, as immunity to one strain does not necessarily prevent a person from being susceptible to a mutated type [17]. However, scientists annually predict which strain of influenza is most likely to prevail, and develop a vaccination for that strain. There are two types of influenza vaccine available, an injection containing a dead version of the virus and a nasal spray containing a live but weakened version of the virus [18]. The vaccine generates an immune response within a person, causing the body to generate antibodies to the virus. However, as the virus is either weakened or inactivated, it does not cause infection but if a live version of influenza A enters the body, the virus will be quickly recognized by memory cells (B lymphocytes) which will rapidly produce antibodies to combat the viral infection.

Treatment of Disease

To combat the infection in cells, different neuraminidase inhibitors can be taken. Neuraminidase inhibitors block the active sites of neuraminidase, preventing sialic acid being cleaved from the host cell, and hence preventing the spread of infection. There are two types of neuraminidase inhibitor: zanamivir (i.e. Relenza) and oseltamivir (i.e. Tamiflu) which can be used to combat both influenza A and influenza B viral infections. Zanamivir is inhaled orally via a Diskhaler and can be used to treat people aged seven and older, and oseltamivir, available as a capsule or powder [19], can be used to treat people aged one and older [20]. According to the New England Journal of Medicine, numerous tests have proved that oseltamivir can reduce the duration of the illness by approximately 30% and the severity of the illness by approximately 40%.
The influenza A virus can also be treated with the adamantanes, amantadine and rimantadine [21]. Amantadine can be used by both adults and children whereas rimantadine is suited to adults aged twelve and over [22]. Adamantanes work by blocking the ion-channels in the viral membrane, preventing the uncoating of the virus so that it cannot release its RNA in to the cell [23]. Influenza A is quick to develop resistance to adamantanes, but rarely develops resistance to the neuraminidase inhibitors, so neuraminidase inhibitors are the more favoured treatment for influenza A. [24]

Conclusion

Although prevention of the Influenza A virus by vaccination is not always successful due to its ability to mutate and therefore cause disease to recur, the treatments of the disease are generally successful, though some more than others. However, neuraminidase inhibitors are in short supply, so the influenza vaccine is still the main method used against the influenza A virus [25], and in most cases it greatly reduces the chances of developing disease. Influenza A is known to have caused deaths in elderly people and children, but overall it seems that if treatment is administered quickly enough, the likelihood of recovery is high.

References

  1. Dimmick, N.J. et al., 2007. Introduction to Modern Virology. 6th edition. Oxford: Blackwell publishing
  2. Childrens Hospital Boston, 2005. Influenza (Flu). [online] Available at: http://www.childrenshospital.org/az/Site1154/mainpageS1154P0.html [Accessed 5 Feb 2010]
  3. Sauter, N.K. et al., 1989. Hemagglutinins from two Influenza Virus variants bind to Sialic Acid Derivatives with millimolar dissociation constants: a 500-MHz proton nuclear magnetic resonance study, Biochemistry, [online], 28(21), pp. 8388-8396,<br>Available at: http://www.ncbi.nlm.nih.gov/pubmed/2605190 [Accessed 5 Feb 2010]
  4. Sauter, N.K. et al., 1989. Hemagglutinins from two Influenza Virus variants bind to Sialic Acid Derivatives with millimolar dissociation constants: a 500-MHz proton nuclear magnetic resonance study, Biochemistry, [online], 28(21), pp. 8388-8396,<br>Available at: http://www.ncbi.nlm.nih.gov/pubmed/2605190 [Accessed 5 Feb 2010]
  5. Nicholson, B.H., 1994. Synthetic Vaccines, London: Blackwell Scientific Publications
  6. Alberts, B. et al., 2002. The Molecular Biology of the Cell. 4th edition. New York: Garland Science
  7. Collier, L. & Oxford, J., 2006. Human Virology. 3rd edition. Oxford: Oxford University Press
  8. Alberts, B. et al., 2002. The Molecular Biology of the Cell. 4th edition. New York: Garland Science
  9. Collier, L. & Oxford, J., 2006. Human Virology. 3rd edition. Oxford: Oxford University Press
  10. Davis, C., 2009, Flu (Influenza, Conventional and H1N1). [online] Available at: www.medicinenet.com/influenza/article.htm [Accessed 10 Feb 2010]
  11. Rahman, S., 2009, Avian Influenza (Bird Flu). [online] Available at: www.scribd.com/doc/21199778/Avian-Influenza-Bird-Flu [Accessed 5 Feb 2010].
  12. Nicholson, B.H., 1994. Synthetic Vaccines, London: Blackwell Scientific Publications
  13. Davis, C., 2009, Flu (Influenza, Conventional and H1N1). [online] Available at: www.medicinenet.com/influenza/article.htm [Accessed 10 Feb 2010]
  14. Treanor, J., 2004. Influenza Vaccine- Outmaneuvering Antigenic Shift and Drift. The New England Journal of Medicine, [online]. 350<ref>Sauter, N.K. et al., 1989. Hemagglutinins from two Influenza Virus variants bind to Sialic Acid Derivatives with millimolar dissociation constants: a 500-MHz proton nuclear magnetic resonance study, Biochemistry, [online], 28(21), pp. 8388-8396,<br>Available at: http://www.ncbi.nlm.nih.gov/pubmed/2605190 [Accessed 5 Feb 2010]
  15. Collier, L. & Oxford, J., 2006. Human Virology. 3rd edition. Oxford: Oxford University Press
  16. WHO, 2013. Avian influenza A(H7N9) virus. [online] Available at: http://www.who.int/influenza/human_animal_interface/influenza_h7n9/en/index.html
  17. Nicholson, B.H., 1994. Synthetic Vaccines, London: Blackwell Scientific Publications
  18. Davis, C., 2009, Flu (Influenza, Conventional and H1N1). [online] Available at: www.medicinenet.com/influenza/article.htm [Accessed 10 Feb 2010]
  19. Moscona, A., 2005. Neuraminidase Inhibitors for Influenza. The New England Journal of Medicine, [online]. 353(13), pp.1363-1373,<br>Available at: http://content.nejm.org/cgi/content/full/353/13/1363#F1 [Accessed 10 Feb 2010]
  20. WebMD, 2008. Oseltamivir or zanamivir. [online] Available at: http://www.webmd.com/cold-and-flu/oseltamivir-or-zanamivir-for-influenza-flu [Accessed 5 Feb 2010]
  21. Moscona, A., 2005. Neuraminidase Inhibitors for Influenza. The New England Journal of Medicine, [online]. 353(13), pp.1363-1373,<br>Available at: http://content.nejm.org/cgi/content/full/353/13/1363#F1 [Accessed 10 Feb 2010]
  22. Winquist, A.G. et al., 1999. Neuraminidase Inhibitors for Treatment of Influenza A and B Infections. [online] Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr4814a1.htm [Accessed 5 Feb 2010]
  23. Moscona, A., 2005. Neuraminidase Inhibitors for Influenza. The New England Journal of Medicine, [online]. 353(13), pp.1363-1373,<br>Available at: http://content.nejm.org/cgi/content/full/353/13/1363#F1 [Accessed 10 Feb 2010]
  24. http://www.who.int/influenza/human_animal_interface/influenza_h7n9/en/index.html
  25. Moscona, A., 2005. Neuraminidase Inhibitors for Influenza. The New England Journal of Medicine, [online]. 353(13), pp.1363-1373,<br>Available at: http://content.nejm.org/cgi/content/full/353/13/1363#F1 [Accessed 10 Feb 2010]
 
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