There are some errors in this lecture – I’ll correct them during the next session.
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We’ve briefly considered the structure of influenza virions and how the viral RNAs can encode one or more proteins. Now we’ll consider how influenza viruses multiply.
Viruses are obligate intracellular parasites: they cannot reproduce outside of a cell. The production of new infectious particles must take place within a cell. Upon entering cells, viruses parasitize the host machinery to produce new viral progeny. The sum total of all the events that take place in a virus-infected cell is called the infectious cycle, or viral replication. Virologists artificially divide the infectious cycle into steps to make it easier to study. The steps include attachment and entry of the virion, translation of mRNA into protein, genome replication (producing more RNA or DNA), assembly of new particles, and release of particles from the cell. We’ll consider each of these steps, and then move on to a discussion of how influenza virus infects us and causes disease.
Today we’ll focus on the first step, attachment of the virion to cells. Here is a typical cell. I’m sure everyone is familiar with it, but it doesn’t hurt to review.
You can see that there is a substantial barrier to anything getting into this cell – the plasma membrane. Viruses have evolved different ways to get around this. But what they all have in common is that virions must first attach to a receptor on the plasma membrane in order to enter the cell. Every virus has a specific receptor that it attaches to, and in turn there is a particular viral protein that binds this cell receptor. Here is an illustration of an influenza virion binding to its cell receptor.
You can see the individual ‘spikes’ on the virion binding to a structure on the cell. The influenza viral spike that attaches to the cell receptor is the HA protein – hemagglutinin. The cell receptor is sialic acid – a small sugar that is attached to many different proteins on the cell surface. Here’s what sialic acid looks like.
On the left is a drawing of a cell protein embedded in the plasma membrane. The interior of the cell – cytoplasm – is at the bottom. Part of the protein crosses the membrane, and there are also parts on the cytoplasmic and extracellular sides. The spheres are sugars that are attached to many proteins (protein + sugar = glycoprotein). Sialic acid is always the last sugar in a chain that is attached to a protein. On the right is the chemical structure of sialic acid; the next sugar, to the right, is galactose. Influenza virions attach to cells when the HA grabs onto the very small sialic acid.
The sugar is actually quite tiny compared to the HA – it fits into a small pocket on the top of the spike. Here is a molecular model showing the HA bound to an analog of sialic acid. The globular top of the HA is at the top of the image. The tiny red and white spheres show where sialic acid would be bound, in a pocket at the top of the HA.
So far we have docked the influenza virion onto the surface of the cell. It’s sitting there quite firmly, but it’s still on the outside of the cell. How does it get in – or more accurately, how do the viral RNAs get into the cell? Stay tuned.