Flu in the kitchen store

A trip with Mrs. R. to buy something for the kitchen doesn't seem to have much to do with influenza virology, but let me try to make the connection. We're at Williams Sonoma. I'm wandering around, idly looking at various pieces of kitchen equipment and thinking random food thoughts. I'm not looking for anything particular, myself. But as I'm cruising by a set of shelves I see it has books on it. Quite a few of them. All about food and cooking and associated subjects, but books. I stop. I start to browse. Fifteen minutes later Mrs. R. retrieves me. She is going to shop for something else. I decide I am going to go to Borders, next door. What does this have to do with influenza?

Now, I have an affinity for books. I suppose that's not quite accurate. My interest in books is more like a pathology, not an "affinity," but I have a reason for using the word affinity besides the fact it makes me sound saner than I really am. In a series of posts I resurrected from the old site (starts here) I discussed some of the intricacies of how the influenza virus finds the right kind of host cell and tissue to infect. Over four posts (lots of pictures) I pointed out that, to the virus, host cells look like a surface covered with a carpet of sugar chains. These chains look like lots of little hairs sticking all over the surface of the cell. The carpet is called the glycocalyx. The chemistry of these chains is extremely varied and the sugars are connected at the cell surface either to fatty acid chains that form part of the cell membrane bilayer (glycolipids) or proteins embedded in, on or through the cell membrane (glycoproteins). I explain it all in tedious detail in the earlier posts.

The virus's surface is studded with a very complex (and large) protein called hemagglutinin, the H of H5N1. It has one spot on its own complicated surface called the active site. The active site has an affinity for a very specific kind of sugar chain arrangement on a host cell, the kind where a slightly modified 9-carbon sugar (sialic or neuraminic acid, it has two names) is at the tip of the chain and its number 2 carbon is connected to another specific sugar, galactose, by a very special kind of link, called an alpha linkage. The alpha linkage can hook to the galactose in different ways. Bird viruses like the linkage to the 3 carbon of galactose, human viruses to the 6 carbon of galactose. These are the α2, 3 and α2,6 linkages you may have heard about (and will learn about in the posts linked to above). Galactose is also linked to other sugars farther in the chain, and the identity of those sugars and the links to them probably are important to whether the virus will easily infect a duck or a goose or a chicken, but we don't know very much about those things yet.

The affinity of the hemagglutinin (abbreviated HA) for the particular sugar chain on the host cell's surface is thought to be quite specific. There has to be a good match between the HA and the sugar configuration (the sugars and their linkages). It is a lock and key set-up. The lockset (the sugar configuration on the host cell's surface) is called the cell surface receptor. HA is the key. The difference between an HA key that fits a bird cell receptor and one that fits a human cell receptor may be only one or two mutations. You get the idea.

Back to Williams Sonoma. Like me, the influenza virus is wandering randomly. The virus is passive. It can't move on its own, isn't "looking for" anything. It is carried by external forces wherever they take it. As these forces take it past a cell, it might brush near the proper cell surface receptor and get stuck there, just as I got stuck in front of the books. The physical connection then entrains a set of biological reactions of the cell, causing the virus to be enveloped by a pouchat the cell's surface. The pouch pinches off to become like a little space vessel in the interior of the host cell. The virus is now connected by its specific affinity to the cell membrane (that's what we call the outer wall of the cell), whose former outer surface is the inner surface of this interior spacecraft. If you are having trouble visualizing it, think of a marble being pushed into the surface of a sealed bag (the cell). Push it in far enough so you can close the bag around in back of it and then pinch that part off so the marble is now inside the bag surrounded by the inside-out bag surface. The virus still doesn't have access to the cell's protein making machinery, which it wants to hijack to make copies of itself. It has to get rid of its space-ship coat. It is this uncoating process which is interfered with by the other major class of antivirals, the adamantanes.

But that's a whole other story. Maybe we'll get to it on another trip to the Mall. Meanwhile, I have a lot of new books to read. Or not. Who's got time?