Lipid Mosaic

Ha ha so somewhere out there in the land of my readers is a secret virus anorak... wanting to know about the attachment of the virus to the cell indeed. Well Ok Mici, let's see what I can do.

I suppose firstly we need to look at the structure of a flu virus (from the Orthomyxovirus family, name derived from the Greek word myxa meaning mucus), and the structure of a normal cell. Of course any mammalian cell with a nucleus will do, or even avian cells. Nucleated - that's the key.

So - let's start with the structure of a cell with a nucleus. And what keeps the nucleus and associated little organelles from spilling into the street is a membrane holding it all together. For ease of understanding how this membrane looks, we can use the now somewhat outdated Singer Nicholson model of a double layer of lipids (fat molecules if you prefer) with islands of protein floating around randomly in this little fatty sea. More bookish anoraks are referred to http://scienceweek.com/2005/sw051223-3.htm where the latest thinking is contained.

The virus however, is slightly different. We already know that the influenza virus has a spiky coat (and just to complicate things the viral genome or set of instructions for making more influenza viruses is split into 8 pieces, and all of these need to be present at once for infection to occur). But never mind all that Dan Brown stuff, let's focus on the way the little bugger gets into the cell.

Mr. Flu is a spiky little bugger, as I will remind you, and looks rather like this http://www-ermm.cbcu.cam.ac.uk/01003465h.htm or like this -
















and also with a bilayered membrane (lipid envelope) surrounding it. The lipids in this bilayer are probably nicked from the previous host cell's membrane (imagine the little baby viruses bursting through the cell walls like that creature in Alien exiting the chest of a hapless crew member - and becoming coated with a layer of fatty slime in the process) but the protein bits are all viral. Not that the cell bursts, you understand - in this particular kind of flu infection and because of the way the viruses leave the cell by "budding" through the membrane, cell integrity is maintained. Viruses that don't need the lipid coat feel quite free to burst the cell as they leave, and can cause spectacular damage.

But I am getting ahead of myself here. First the virus must attach to the surface of the cell membrane. This is unaffected by temperature, but strongly sensitive to pH (occurring best at neutral pH), implying some sort of electrostatic binding between the amino groups on the virus protein spikes and the acidic phospholipids of the cell membrane. In fact, as is common with many viruses, the binding occurs with something called sialic acid (also known as 5-N-acetyl neuraminic acid and I just know that many of you will be spotting the link to the viral spike neuraminidase already..).

So the virus kinda drifts up against a cell - attracted by electrostatic forces to the appropriate sites on the cell membrane where exactly the right bits lock together. Haemagglutinin (thus named because it can cause clumping or agglutination of red blood cells, a useful trick for a virus to have) locks onto the correct receptor site of sialic acid and then, perhaps assisted by our old friend neuraminidase here although evidence is sketchy, the cell's membrane becomes a little more flexible and the virus slips through by a process called endocytosis. That means the whole virus enters the cell, not just the RNA instructions (some other viruses operate in this second way, injecting their replicating code into the cell while leaving their capsule outside). But the important point is that the fatty cell membrane becomes more easily penetrated and the virus sinks into it and then through into the cell.

In some cases the flu virus may, for reasons best known to itself, decide not to infect the cell after attachment. This is when the neuraminidase spikes come in useful - neuraminidase as mentioned before is an enzyme and has the specific function of cleaving neuraminic acid, so the virus can then disengage and drift off again. Usually, however, the process unfolds normally, virus enters cell, the little packages of RNA instruct the cell to stop making its own proteins and start making the building blocks of more viruses, the blocks drift together and assemble into finished examples of Orthomyxoviridae, loosen the cell membrane from the inside now with judicious applications of neuraminidase and then pop out through this Singer Nicholson lipid mosaic membrane that started the whole rambling blog entry...

Sheesh. It's been a long time since Microbiology III (23 years to be precise) and I must admit to needing to refresh my knowledge a little. Useful sites include http://www-ermm.cbcu.cam.ac.uk/01003465h.htm and
http://www.pnas.org/cgi/content/full/100/25/14610

I didn't go into any detail on which body locations have cells with more or less receptors for different kinds of H spikes - but you're welcome to check that out yourselves. Of course different species will have different receptor concentrations so infection may occur by inhalation, ingestion or other methods depending on where in the body the cells are with the most amount of the right receptors for that kind of virus...

Have fun and try not to cuddle any chickens