28 December 2009

Retrovirology: Part two

Please know at the outset, I am not an expert on this. The information I have used is summarized from my anatomy and physiology books I used in my University days, which I have referenced at the end.
What, exactly, is a retrovirus?
Like many people, when I first learned about the research findings regarding XMRV and its potential role in CFS, I immediately wanted to understand a bit about retroviruses. I’m naturally a scientifically orientated person; I like not only knowing what something is, but also 'why' it is, and 'how' it works. I know there are others also interested in the 'what’s, whys and how’s' of things such as this retrovirus, ESPECIALLY when it appears to have suddenly affected us directly. I understand, however, that not everyone considers a textbook good quality bedtime reading, like I occasionally do! And when I’m really exhausted, I need something that’s accessible to read, either summarized or written in easy to understand terms. I figure that if I benefit from summarizing what I learn about retroviruses for myself, it may also be of benefit to others.
Part One: DNA to DNA replication (parent to daughter cells – sorry guys)
As I vaguely remember, school taught me that my body is made up of organs, which are in turn made up of millions of cells. Inside every one of my cells is a copy of my individual genetic information, which 'codes' for each of the protein molecules needed to build my specific characteristics and features. This information is held in the centre, or nucleus, of every one of my cells, a fact which is exploited in many crime shows on TV, where the good guys find the bad guys by identifying their bad-guy-DNA in a strand of hair, or drop of blood.
These cells of mine are replicating constantly, as is the all-important information code held within them called DNA. This cell division process is called mitosis (except in sex cells, but that’s a story for another time). Many of us are familiar with the wound up ladder image of DNA, called a double helix, which resides, curled up tight, in the nucleus of a cell. Every time a parent cell replicates, (creates an identical copy of itself by going through the process of cell division), it must also replicate this precious cargo, the DNA. To do this, the DNA unwinds, and begins to separate at one end of the ‘ladder’, right down the middle of each 'rung’, so we now have two 'half-ladders’ at one end of the unwound DNA strand. Each of these ‘half-rungs’ along the length of separated DNA is a molecule. These individual molecules are called a ‘nucleotides'. Both of these half-ladders of nucleotides are now ready to act as templates for replication. An enzyme, 'polymerase', (a blue-collar worker), speeds in wearing his sweat bands, and starts frantically matching new, individual, nucleotides to the original, exposed nucleotides of each one of the 'half-ladders’ of original DNA, which leads to the rebuilding of TWO whole (and, of course, identical) ladders of DNA once again . Eventually, these ladders coil up again into two strands, and link at the centre, forming a pretty standard X-shape. We can now call this pretty standard X-shape a chromosome. When the parent cell divides into two, it pulls apart our standard X-shaped chromosome, so that each daughter cell ends up with one ladder of DNA, at which point the process begins again. But this is not the only form of replication that occurs.
Part Two: DNA to RNA replication (Protein synthesis)
As mentioned previously, my individual DNA stores the information on how to build each specific protein molecule my cells need in order to function, and on a grander scale, these proteins dictate my characteristics. The problem is my DNA never leaves the nucleus of a cell. Therefore, I need something to go on an adventure into the cell nucleus, to get the information off the DNA and translate it into protein molecules. RNA is up to the task. During a process called transcription, RNA builds up a copy of the DNA strand inside the nucleus, in a similar manner as when DNA replicated itself. The DNA ladder uncoils and splits down the centre of each rung for the length requiring. Once the RNA has finished making a copy of the DNA, it gracefully exits the nucleus. Once the RNA is outside the nucleus, it begins the process called translation, where the RNA strand is literally translated into the specific proteins molecules that underlie all cellular activities. So what does this have to do with a virus?
Part Three: Virus and retrovirus replication

Viruses are super tiny obligate parasites, meaning that they require a living ‘host’ cell in which to replicate. Aside from being so small, they are also rather simple in their structure. A virus is a strand of either DNA or RNA, wrapped up in a protective protein coat, and some also have a fatty envelope which provides added protection when they are outside of host cells. Unlike cell division, viruses replicate by using the mechanisms available in a host cell. So, a virus comes up to one of my healthy, living cells and enters through the cell wall, or injects its genetic material into the cell (as is the case for bacteria cells). The virus then manipulates the replication machinery of the my host cell, if it’s genetic code is DNA, it enters the nucleus of my cell and makes copies of itself in the same way my own DNA replicates, as described in part one. (If it’s genetic code is RNA, it replicates outside of the nucleus, and may or may not create proteins). When the virus completes its replication, it exits the cell by bursting the cell membrane and killing the cell.
The retrovirus is an RNA virus, however, instead of creating copies of its RNA in my host cell, it uses an enzyme called reverse transcriptase to produce DNA. (If you remember in part two, this process usually works the other way, and my DNA code is copied by the RNA and used to produce protein molecules). This DNA copy of the virus is then incorporated into my DNA genome, residing in the nucleus of my cell, and replicates, along with the rest of my genome, during each cell division process.

It is suggested that up to 8% of the human genome has been acquired over the generations through retroviruses, however much of this genetic information does not appear to code for anything and is thus called ‘junk-DNA’.

I hope that some of this is helpful, and gives a little insight to the processes going on at a molecular level, for those interested. If there is anything you wish to add, change or remove, let me know, or if you want further information, contact me for a list of references.

Gallo, R, C., (1991). Virus hunting AID’S, cancer and the human retrovirus: A story of scientific discovery. USA: BasicBooks.

Marieb, E., (2001). Anatomy and physiology (5th ed.). pp 94 – 109. USA: Benjamin-Cummings pub co.

3 comments:

  1. Excellent - thanks. Can I post this in the Phoenix Forums - attributed to you of course.

    ReplyDelete
  2. 11 December 2009:

    http://forums.aboutmecfs.org/showthread.php?p=21640&posted=1#post21640

    =)

    ReplyDelete
  3. Thank you!!! Before reading this, I haven't been able to understand retroviruses - (retrovirii?). Thank you for pacing yourself enough to write all your posts. That's a very generous gift.
    One of my brothers has been severely disabled from ME/CFS for nearly 20 years. He was homeless for a few years, and none of us on the other side of the country had any idea what he really was going through. I didn't understand until he came to live with me. My brother is highly intelligent, and I'm no dummie, but dealing with his brain fog and his awful fatigue was a pain in the neck AND a source of great amusement to both of us once we found that item that he had misplaced. I wrote an ebook that is his story - and the story of how what he & I had to adapt in order to live together reasonably. I'll have to update the book now that I have some way to explain how a retrovirus works.

    I shared your blog on my facebook page. It's still tough to get nonPWCs excited about ME/CFS or XMRV - the disease is just too unknown among the public. Thanks for your clarity and diligence in your research and your writing.
    xo

    ReplyDelete