[Back in January we did a series of posts on the old site giving some background science on the influenza virus for the general reader. The Reveres are traveling (for a change) and so we thought it was an appropriate time to dig around in the old archives and update some of the posts thought useful by readers. Here’s the first installment of a set of posts on cell surface and HA protein of the influenza virus and where they fit in the picture. Links to all four posts: part I, part II, part III, part IV]
Avian influenza, as its name suggests, is a disease of birds. Most aquatic waterfowl seem to tolerate infections with the virus with little difficulty (there are exceptions, especially with H5N1), while terrestrial poultry seem to do very badly, indeed. The H5N1 subtype of the virus also infects other animals, including mammals like cats, dogs, ferrets, horses, pigs and humans. Most readers here know that the H and N designations refer to the proteins on the outside of the virus but don’t know much about the general subject of lipoproteins, so these posts will be for those of you who want to know a little of what this is all about, especially how this is related to things like what animals can be infected and how the immune system responds to different viral strains. For a lot of you this will be much more than you want to know, but there are a number of lay and professional (but non-specialist) readers of this blog who have become quite knowledgeable and this is meant to provide some additional background. So we’ll start at the beginning.
The influenza (or any) virus needs to get inside a host cell in order to make new copies of itself. Reproducing is essentially its only task in life. We know that viruses and other pathogens don’t usually infect all animals (they have a specific host range) and within an animal, usually infect only specific tissues. So cells from different animals and different tissues must somehow look different to the virus. How does a virus “recognize” the right cell? Although we are leaving out a lot of details, there is still much we need to discuss.
Since the virus first “sees” the cell from the outside, we start at the cell surface or cell membrane, as it’s called. Animal cell membranes have a very complicated structure but essentially they consist of a supporting structure, called a lipid bilayer and various bits and pieces sticking on, in and through it. Below is a picture of a lipid bilayer, the structural stuff. (I copped this from a nice set of 1997 lecture notes by Prof. Steve Downing at the University of Minnesota-Duluth. This is copyrighted material, but I am not making any money from it and if the Regents of the University of Minnesota want me to take it down I will, of course. I doubt they care and are probably grateful for the free publicity.)
You can see the reason it’s called a bilayer (it has two layers). Each little building block consists of two long fatty chains (the black bars) joined at the end by one of the colored balls. The fatty chains don’t like to mix with water and face each other in the interior of the membrane, while the colored balls don’t mind water and line both the interior and exterior of the cell. The reason the diagram has different colored balls is that these building blocks can be of various kinds (called phospholipids).
Besides the phospholipids, there are also a fair number of glycolipids. They aren’t shown above because I wanted to keep the picture clean. Whenever you see the word “glyco-” attached to something you should be thinking sugars (carbohydrates). Lots of the building blocks have sugars on them. Attaching a sugar is called glycosylation, and the thing that has the sugar attached is said to be glycosylated (and often the location of the attachment is given). Here’s a closer view of a glycolipid, showing some of the molecules (there are four different glycolipids shown in the four corners, each with different numbers of sugars attacked; in the middle is a blow-up of the one at the upper left showing a single sugar attached to the two long fatty acid chains shown as black bars in the other pics):
The previous picture of the bilayer didn’t show any of these guys (the round colored balls are all phospholipids), but the membrane has these kinds of building blocks, too, although fewer of them. Here is what it looks like when we add these glycolipid building blocks to the structural membrane bilayer:
Those colored hexagons are different kinds of sugars and they are strung together in chains (the little pink squiggles are cholesterol and we don’t need to discuss them here). Chains of sugar building blocks (the block units are called monosaccharides) can be oligosaccharides (when there are only a few of them), polysaccharides (when there are many building blocks, often in the form of oligosaccharide units strung together) or, more generically, saccharides, sugar chains, or glycans. The variety of terms can be confusing, so we are taking the trouble to set it out here, as they often appear in the literature. See here, for some (very technical) guidance.
So we have fats and sugars here. What about the third food group, proteins. Yes, lots of them and of various kinds and configurations with respect to the cell membrane. They can be bound either to the inside or outside surfaces, be tethered to the membrane and stick out in either direction, or wind their way back and forth through the membrane surface with loops and ends sticking up on either side or both. The proteins can be globs, oblongs, long threads or other complex shapes, but whatever their shape, they are long strings of amino acids (folded into the various shapes) and have two ends, one called the N-terminal end, here designated -NH2, and the other the carboxyterminal end, here designated -COOH. And it turns out these protein molecules also have sugars hanging off of them (the colored hexagons again), i.e., they are glycosylated. Here’s another cartoon picture illustrating an example:
From this you can see that the cell surface will have a lot of sugars (carbohydrates) studding its surface, some from the glycolipids and some from the glycoproteins. Together they form a dense “canopy” of sugars (like the tops of the trees in the rainforest) called the glycocalyx. The glycocalyx of a cell is invisible with usual microscope techniques, but special procedures can bring it out. Here are some examples, taken from a wonderful (but very technical) website of Dr. Kevin J. Yarema at Johns Hopkins:
The picture in the left panel shows a cell surface with a fluorescent tags on the glycans to make them visible. The middle panel has a glycocalyx brush border (the hard to read label with two arrows). The right panel shows the glycocalyx looking like a lot of hairs sticking up from the cell surface.
So we’ve arrived at this point. The cell surface has a lot of sugar chains of various kinds covering it and sticking up around it. This is the surface various pathogens (including the influenza virus) “see” and which determines which pathogens will glom on to which cells.
We’ll press on with more details in the next post.