Wednesday, February 02, 2011

DE-MYSTIFYING AIDS

When I was little, my father brought home a book about atoms, very simplified, and I struggled my way through it, believing that I could understand it.  (My family believed that anyone who could read had access to the key to the universe.)  Since then I’ve always had a clear mental picture of a cluster of balls with balls zooming around it -- a sort of solar system of entities.  Quite inaccurate but useful.
In grade school we all saw a Disney movie about how vaccination works:  little spiders get into your body and victimize the little round red blood cells, so white blood cells attack them, wearing Civil Defense helmets.  The vaccine was little green turtles that the white blood cells could use for target practice.
So I approach the task of understanding one HIV particle at about that level of sophistication.  This is probably a force for good, since I expect much of my readership is in about the same state, but it also means that I might get things wrong by oversimplification and misapprehension.  (Big words for dumb mistakes.)
First, one must start way way back at the beginning of life.  Living things (organisms) are composed of self-replicating protein processes.  A protein is a complex organic compound that includes carbon, hydrogen, oxygen, nitrogen and sulfur.  Proteins are organized (note!) into a-amino acids joined by peptide linkages.  Twenty different amino acids are common building blocks which the protein organizes (there it is again!) into enzymes, structural elements, hormones, immunoglobulins, and so on.  That’s what a body is made of, what runs it, and what reproduces the original blueprint in a new body plus whatever everyday new cells need to be made. 
The reproduction code is carried in every cell’s nucleus.  (A few cells like red blood cells don’t have nuclei.)  The code is arranged in pairs on strands called chromosomes, along which are the genes  which are always one of four kinds, assigned letters the same as the notes of the musical scale.  Genes “shake hands” between the two chromosome strands.  (Because of assigning letters it is possible to play a genome as music, which is interesting but not helpful.)  The genes are shaped like a double helix (twisty) and around them is a epigenome.  Imagine two grand pianos onstage and backed up to each other (chromosomes) and around them a full orchestra (the epigenome which is also protein).  Everything that gets expressed in the body in terms of what it does and how it renews and protects itself all goes back to these mechanisms.
Bits of genomic instruction can jump between creatures, either plants or animals.  We call them viruses.  The viruses of other creatures can jump to us because of proximity, because of breathing them, because of ingesting them, because some vector like a flea carries them across.  Ten thousand years ago when animals were first domesticated a LOT of viruses jumped.  Think cowpox-to-smallpox.  A few years ago a virus called “West Nile Virus” got into the mosquitoes from birds.  Now ranchers must inoculate their horses every spring to protect them.  One in 150 infected people will get very sick from this “neuroinvasive” virus which afflicts horses and cats more than other species.
The zillions of genes on human chromosomes may include more code left over from past invasions than code that actually makes and maintains the body.  Recently some “fossil” genetic material from the HIV “family line” turned up in lemurs in Madagascar, possibly 65 million years old.  It’s dormant in their systems -- doesn’t do anything.  About one in a hundred humans, usually with northern European bloodlines, is naturally immune from HIV-AIDS.  This is thought to be the result of a very ancient plague.  But people who are immune to HIV are unusually susceptible to “West Nile Virus.”
How this immunity is achieved, we all want to know.  It helps to have a mental picture of a virion, which is one particle of the virus, outside a host cell and surviving in crystalline form, capable of infecting a cell.  A crystal is “a naturally produced angular solid of definite form.”  Crystal: not living.  Virus: border state.  Cell: living.
Two kinds of nucleus are in a virus:  DNA, or deoxyribonucleic acid, is the hereditary code in humans and almost all other organisms.  To to  http://dnaftb.org/  to see helpful stuff (cartoons!).   Like DNA, “RNA is made up of a long chain of components called nucleotides. Each nucleotide consists of a nucleobase (sometimes called a nitrogenous base), a ribose sugar, and a phosphate group. The sequence of nucleotides allows RNA to encode genetic information. For example, some viruses use RNA instead of DNA as their genetic material  (we call them “retroviruses”), and all organisms use messenger RNA (mRNA) to carry the genetic information that directs the synthesis of proteins.”   
In short, RNA is a template for DNA.   Diagrammed, the virion looks like a sphere in a sphere:  a lipid (fat) membrane with a lot of protein “binders” or ports on its outside, an inner “capsid” (capsule of protein) which has inside it the actual RNA.  It works by getting that RNA template into a cell.  How it does that is of great interest.  It appears that the people with natural immunity (achieved because of two missing genes, a matched pair from both sides of the double helix) have no protein of the kind that would allow attachment and (ahem) penetration.  Researchers have figured out how to design siRNA (short interfering RNA) which turns the code against itself.  It’s possible but expensive.
There are “kinds” of RNA virus.  One way it is different is that it is “lente” -- not shaped like a lens but slow as in music.  This means that it was “under the radar” for a long time, simmering along in the African jungles, killing people who were “nobodies” in terms of modern medical awareness, probably getting it by killing chimps and certain monkeys for “bush meat” without any way to make the connection between illness and source, feeling cursed.   Their exposure would have been increased by the ecological displacement of growing populations, needing more food.  Undiagnosed and invisible, the viral code must have moved from village marketplaces to people brought in by tourism or pushed out through migration to cities, and then to white populations who are alert to their health and insist on diagnosis and care.  Even there it was a mystery for years.  Through blood exchange -- far more common in many ways than people had thought about -- the virus has spread around the planet.  There is no cure.  So far.  
The structure of the RNA is in threes, I guess, though the list looks much longer to me.  It’s not spiral nor double, but jaggedly folded.  The gag gene “provides the basic physical infrastructure of the virus.”  The pol gene supplies the basic mechanism for reproduction.  Other named genes are env (envelope), tat, rev, vpr, vif, nef, pvu, and tev, which is rare.  These bits have been mapped and photographed, both as whole strands and as little segments, but knowing which atoms are where in the protein doesn’t quite show how they interact in process.  It’s the process we’re after.  We ARE process.
What I’ve tried to do is to de-mystify this infectious virus, to “take the juju out of it,”  the curse off it, so that it’s no longer a matter of superstition and “magic.”  Getting it under control is a matter of practical good planet-keeping.  Otherwise, our planetary overpopulation problem will resolve itself, perhaps leaving alive only one out of a hundred of us.  

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