Case 1- Fresher's Flu Flashcards
What causes the flu?
Influenza A and B viruses cause ‘the flu’ in humans.
What are the membrane glycoproteins of influenza A and B?
Influenza A viruses have three membrane glycoproteins; haemagglutinin (HA), neuraminidase (NA) and Matrix-2 (M2). Influenza B viruses also have HA and NA, as well as two other membrane proteins.
What are current influenza subtypes in humans?
Influenza A and B cause the same spectrums of disease. Current circulating Influenza subtypes in humans (seasonal flu) are H1N1 and H3N2.
What is influenza C?
Influenza C is structurally different to A and B. Nearly all adults have been infected with influenza C virus, which causes mild upper respiratory tract illness (like the common cold). Lower respiratory tract complications are rare.
What is Haemagglutinin (HA)?
It is an influenza membrane glycoprotein that acts as both an attachment factor and membrane fusion protein. There are at least 18 types of HA and not all are able to facilitate entry into human cells. Types 1-3 are those typically found in ‘human’ Influenza viruses. H5 seen in avian flu (H5N1) was not previously able to infect humans – however single amino acid changes allowed it to. H7 has also been seen to infect humans.
What does Haemagglutinin bind to?
It binds to sialic acid on the surface of target cells, allowing the virus to enter the cell. Sialic acid is present on erythrocytes, upper airway and lung endothelial cell membranes. Binding to sialic acid on erythrocytes results in haemagglutination, which creates network/lattice of interconnected RBCs and virus particles.
What is neuraminidase (NA)?
It is a membrane glycoprotein that acts as a glycoside hydrolase enzyme. It cleaves the sialic acid side groups from glycoproteins, which is essential to allow viruses to be released from cells, and go onto infect other cells. If not for neuraminidase, HA would remain bound to sialic acid and the virus attached to the cell. There are at least 9 types, with some variants being more virulent than others.
What are the two mechanisms that allow change in genetic material in viruses?
1) Antigenic drift: natural mutation over time and happens continuously, in all viruses.
2) Antigenic shift: requires genetic reassortment and yields a phenotypic change. This term is often applied specifically to Influenza.
What is antigenic drift?
It is a natural mutation over time of a known strain resulting in small genetic changes, which initially result in viruses with the same antigenic properties and therefore the immune system still recognising it. However, the accumulation of small genetic changes over time can produce viruses with slightly different antigenic material, meaning people can become susceptible again. Antigenic drift therefore may lead to a loss of immunity or to vaccine mismatch (hence need for yearly new influenza vaccines). Antigenic drift occurs in all Influenza subtypes.
What is antigenic shift?
It is an abrupt, major change in genetic material, that only happens in Influenza A (other types of Influenza are not able to infect other animals - which is essential for allowing reassortment). It leads to the formation of a new Influenza A virus subtype, or a virus with a haemagglutinin or a haemagglutinin/neuraminidase combination that has emerged from an animal population that is so different from the same subtype in humans that most people do not have immunity to the new/novel virus. The genetic change confers a phenotypic change which requires an entirely new antigenic response. Therefore, when shift happens, most people have little or no protection against the new virus and the population is at risk of a pandemic.
Outline the mechanism of antigenic shift
When two or more different strains of a virus infect the same cell, their genetic material can combine to produce progeny with new HA/NA combinations (a mixture of the original parent strains). Human cells can only be infected with viruses that display certain haemagglutinin molecules (typically H1, H2 or H3, but other types have been seen to as well). Numerous other HA types are seen in and come from birds, not all of which can infect humans. Pigs, however, can be infected by both human and avian strains of Influenza A. Pigs can therefore act as a reservoir for genetic reassortment of Influenza A HA/NA genetic material because influenza viruses capable of infecting humans can reassort with new genetic material from the avian influenza pool.Therefore there is scope to produce dangerous new virus subtypes that are a) able to infect humans and b) have genetic material new to humans.
Does antigenic shift mean a complete change in NA/HA subtypes?
Not necessarily, as you can get antigenic shift and (therefore a pandemic) without a number change, if the new antigenic material is strikingly different to the old material. For example, humans were historically exposed to H1N1 Influenza A (Spanish Flu 1918 - 1957). In 2009, an H1N1 virus with a new combination of genes (and therefore antigenically very different) emerged to infect people and quickly spread, causing the Swine Flu pandemic (so named because it was similar genetically similar to an H1N1 virus seen recently in pigs). In this case the new H1N1 causing swine flu would still be considered to have ‘shifted’, despite having the same HA/NA subtypes as a previous strain, because the antigenic material was so different and was likely obtained from reassortment of genetic material in pigs.
