Essay Example on Influenza virulence Strategy

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Influenza virulence strategy The enveloped influenza virus causes yearly seasonal epidemics and also sporadic pandemics in humans causing 250 000 to 500 000 deaths per year world wide The virus can be distinguished by antigenic differences between the virions nucleocaspid and matrix proteins influenza A which is responsible for the periodic flu outbreaks influenza B can also cause these same outbreak pandemics and influenza C causes only mild upper respiratory tract illness Influenza A which has greater amino acid variability can be further sub divided by the properties of the two different viral envelope proteins the two viral glycoproteins that are embedded into the virion include the protein haemagglutinin homotrimers HA1 18 and neuraminidase homotetramers NA1 11 which are found on the surface of the influenza virus in the abundance of 4 1 respectively These aswell as eight other proteins PB1 PB2 PA NP M1 M2 NS1 and NS2 are all encoded by the eight single stranded RNA molecules of the segmented viral genome within the nucleocaspid except for influenza C which has a segmented genome of seven ss RNAs these encoded proteins all have a role in the influenza virulence strategy and life cycle 



The influenza A virus uses the viral attachment protein HA to act as a viral ligand toward the sialic acid moiety of glycoproteins within the plasma membrane of columnar epithelial cells causing viral adherence within the host respiratory tract Thus these host cells will only be susceptible to the viral infection if the respective viral receptor is present aswell as functional However the affinity of HA to sialic acid within humans is low but as there are multiple low affinity HA sialic interactions this will lead to a virus cell interaction of high avidity The use of this highly ubiquitous and abundant receptor molecule is important as it defines the strain of virus that the host is subjected to for example in human strains such as H1N1 there is a higher specificity of HA to sialic acid bound to galactose with an alpha 2 6 linkage as there is a high abundance of this sialic acid linkage within the upper respiratory tract URT thus the viral receptors are determinants of viral tropism On the other hand Avian viral strains adapted to birds such as A H5N1 which can be transmitted to humans contain haemagglutinin with a preference for the alpha 2 3 linkage which are predominantly located within the lower respiratory tract LRT of humans e g the bronchus and alveoli At both points within the respiratory tract the mucosal membrane is damaged and evaded as a result of the neuraminidase actively cleaving sialic residues from glycoconjugates allowing the degradation of the mucus and the ability of influenza to reach the epithelial lining of the respiratory tract and causes the translocation to the lung where it then undergoes proliferation and causes infection 



Pneumonia where there is a rapid onset of fever bloody mucus difficulty breathing cough and generally feeling unwell Once the viral receptor recognises its viral ligand the virion is internalised into an early endosome by clathrin mediated endocytosis where protons are introduced and the late endosome has a decreased pH the acidifying of the endosome causes the conformational change of the HA timers into HA1 and HA2 sub units whereby HA1 opens and allows HA2 to form a triple alpha helix bundle which extends to the endocytosed membrane and causes fusion between the viral and endosomal membranes Before the viral RNA can be released the M2 channel is activated upon this low pH allowing the acidification of the viral envelope by the movement of H ions through the channel this causes a weakened bond between the M1 and ribonucleoprotein complexes and subsequently there is the release of the negative stranded 8 ssRNA segments into the cytoplasm of the host cell where they translocate into the nucleus for the process of transcription and translation by RNA replicases The viral specific mRNA is transported out of the nucleus and translated into the viral proteins where they move to the plasma membrane as newly developed virions and release via budding as pleomorphic virions This process of release is facilitated by the slower acting viral envelope protein neuraminidase thus acting primarily in virus assembly

 The protein is inserted into the host plasma membrane before the virion buds off this allows the proteins to remove the terminal sialic acid from the HA ensuring the virion can bud off successfully and infect neighbouring cells aswell as preventing the re binding of the newly synthesised influenza progeny As influenza virulence is mediated by its glycoprotein haemagglutinin it is this antigenic nature of this protein that allows the host to recognise pathogen associated molecular patterns PAMPs and thus cause a humoral immune response in the context of neutralising specific IgA antibodies To ensure immune evasion influenza epidemics are associated with changes in its antigenic structure due to both random mutations antigen drift within the antigenic HA and or NA and selective advantage of a strain of influenza virus that is not effectively recognised by the host immune system antigenic shift as a result of the unique function of influenza A segmented genome resulting in seasonal variation of influenza pandemic strains The combination of the antigenic changes allows influenza to evade the B cell mediated response but causes problems with vaccinations for influenza as strains constantly change antigenic protein presentation so effective vaccines for an old strain will not be effective against a newer strain


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