Panama Story-Chapter 8
Chapter Eight

A Replicating Viral Journey, though a Hepatocyte

In this chapter we are going to go on a genetic field trip.
We will become micro-geneticists, enter a liver cell, and watch how the virus operates.
We will have to be shrunken down to the size of a virus - approximately 50 nanometers.


As we enter the blood stream note that we must elude the white blood cells. If one of you readers are swarmed by a group of macrophages then "you're on your own"! As we arrive into the liver notice how it resembles a suburban neighborhood. Major routes of blood transportation branch into smaller ones, that branch even further. The liver is a strange and wonderful organ that is yet to be fully understood. Each liver cell is actually a small liver in itself. Each house in suburbia looks pretty much the same, well the liver cells are all exactly alike. The cells are connected by a communications network (apoptic) that is not fully understood.

When a liver cell dies the other living cells divide and quickly replace the dead one. When many cells die, and there are only a few scattered cells remaining, this communications network announces "grow!". The cells somehow know that they must increase their rates of growth and cellular division, dramatically. The little liver cells try "mightily" to keep you alive. There is a point reached that they can no longer do their jobs, as
functioning liver cells, and they begin to die, also. Before they die they multiply rapidly to compensate for the
body's needs. As the neighborhoods are destroyed, so are the roads that supply them. The supply of oxygen
and nutrients can not reach the "neighborhoods" or individual cells (houses). It eventually becomes like a city being supplied by one dirt road - into and out of the city. The city would soon be strangled to death with traffic on this roadway. This is comparable to "portal" back pressure. The main "Interstate" highway into the liver is called the "portal artery". If your portal artery becomes clogged, or backed-up with pressure, then then the city (your liver) will rapidly deteriorate and die. We can not live without our livers. We need them to fight disease, store iron, build lipo-membranes, destroy old un-used parts and reconvert them into good building blocks for protein manufacturing use. The liver also stores "ready energy" for the body in the form of "glygogen". Glycogen is just the molecule that is the body creates in order to store sugars in the liver. The liver is also involved in a host of other functions that provide life support - to you.

Nutrient rich blood from the digestive tract flows through (profuses) the liver like a filter, or sieve. The blood
flows from the stomach and intestines through the liver and then back up to the heart, over to the lungs- gets rid of bad carbon dioxide and then picks up good fresh oxygen. The oxygen is then brought back to the heart and back out to the body again. We will follow the blood vessels through the liver and turn to the left, here, and go over to this side area. As we pass neighborhoods it appears that each block is having a block party. "Hepato-citizens" are scurrying in and out of the cells with objects in and all about. It appears to be chaos! But the closer we look, we see that, all is actually very well organized! Every worker in the cell has only one job to do. Each worker is designed and trained to do only one job. They bring one object in from the blood stream to the cell and then come and get another object to bring in. Or, they bring an object out into the parade (bloodstream) and release it. Away it flows to the heart. We go from large neighborhoods into smaller and smaller ones. Finally, we reach a single block of cells and we find one cell to our liking. It looks like an octagonal fish tank. One by one we slip tightly through a hole in the cell membrane wall and while holding hands proceed in a single file as we enter.

As we enter the cell make sure to let the "guard molecules" see your "identification" or they will not let you
in. If you lose it once inside they may not let you out! Again, "you'll be on your own" once more! What we see
inside the cell resembles a huge construction site. There is constant building and demolishing going on
around us. There are hundreds of new structures being built by crews of workers. Some structures are almost completed and others are in varying stages of completeness. In some areas they are simply restoring old structures, and in others, they are right- out breaking and smashing them up. There are supervisors running around instructing workers, and trucks of supplies keep coming from the center area of the cell site. We head to the center where the nucleus is. You can tell that the big boss is in there, it looks like a Corporate Headquarters! As we approach the wall of the nucleus we see a HBV DNA Virus knocking on the door of the nucleus wall. Like "Dorothy" from the "Wizard of Oz" banging on the city of Oz's front door. The virus does not know the secret code word, but we do! We whisper to the HBV virus, "tell them Adenovirus sent you". At that point another virus materializes from behind the nucleus.

"Who Called my Name?" the Adenovirus bellows! The HBV virus says, "me!" The adenovirus looks at HBV and recognizes and old friend!

"B !, you're back! and you look a little different this time." The Adenovirus compliments the HBV on its "yellow" radiance.

Remember this HBV has a friend with it. But the friend is very angry. Apparently the friend "C" has been tied
up for decades. Once released the virus will make up for all its inactivity over the last half century. The last half of the American Century.

The Adenovirus has manners. It escorts us (transport RNA) into the nucleus one by one, and closes the door
behind us as we enter. Notice that once in the Headquarters you can see out into the cytoplasm. From the
outside you could not see into the nucleus. You can watch all the activity from inside here, as the big boss
does. You notice a huge set of "blueprints". They contain all the instructions for the activity going on in the
cell. We get a quick tour of the cell nucleus before there is a problem. A hostage situation is developing. It
appears that HBV's friend, Yellow Fever, has escaped as a mutant and is holding the big boss hostage. The
Adenovirus is in on this. The adenovirus forces HBV into the blueprints (HBV integrates into the DNA genome
of the liver cell). Adenovirus is a brute! It rips the HBV zipper wide open, exposing both sides of the zipper.
HBV can do nothing, it is stuck in the blueprints.

All liver cell workers can now tell that the big boss is in trouble by the wailing siren resonating throughout the cell. The Alarm has been triggered by a bodyguard (messenger RNA) for the big boss (the entire human DNA genome, or: chromosomes). The nucleus' workers see the big boss in trouble and they do what ever the
Adenovirus says to do! Adenovirus orders the nucleus cell workers to start grabbing "nucleotide" building
blocks and to "reform" each side of HBV's open zipper. This they do quickly. The blocks are lined up in a row
all long the two edges of the zipper ultimately creating "two zippers". The newly created zippers are then
ripped off again (encoded) and taken to the cytoplasm. They are inverse "copies" of HBV. Once in the
cytoplasm, more Adenoviruses surround the newly formed copies. They beat them up and tie them together.
Now the "string of Nucleotides" is ready to be copied. But it is not very stable. It was not created through
millions of years of evolution. It has not been "hardened" to the real biological world. Adenovirus now instructs cytoplasm assembly line workers to start manufacturing (encoding) the virus! This they also do quickly.As the virus is produced (another zipper is formed) other workers are instructed to pull the zipper apart again completely. Once this happens a new creature is formed. A Frankenstein monster of sorts. A man made virus. A genetically engineered RNA sequence. When Frankenstein appears it scares the adenovirus into working for it now. The new virus tells all "call me HCV"!

HCV forces the cell workers (messenger RNA) to make many copies of itself quickly, so fast in fact that a few
are made wrong. These wrong copies (mutants themselves) continue to have reproductions done of
themselves, compounding the errors - genetically. Over the period of ten orr twenty years many mutants,
variants, or quasi-type species arise. Some move to other parts of the body to setup housekeeping. Some
move into the joints, others into the sinuses, and still others float around causing trouble (gang-related
problems). The viruses leave the cell by budding out and then entering neighboring cells (a neighborhood riot begins). The entire area starts to swell with activity, onlookers, and riot police. Eventually the entire liver will swell, or become inflamed. This is the first "stage" of liver disease.

When the cellular alarm was triggered Interferon police were called in. Remember Interferon is produced in the liver cell, it was one of the construction projects that we saw being built. Gamma Globulin, or Gamma
Interferon are one in the same. They are the cytoplasm's cellular line of defense "police". However, they only
can arrest HCV. They do not know what the "variants" look like, and remember everyone has only one job to
do in the hepatocyte. The mutants are "undercover" viruses. They escape detection by many immune police
because of their ability to change disguises and become different looking creatures - but still "Frankensteins"!

We must leave the cell now, as you can see they are very busy in here fighting this virus. We will exit this way
into the blood stream and be carried to the heart. From the heart we'll go to the lungs and then back to the
heart. We know there is a deep cut in the finger tip of the left hand, so if we move quickly we will be able to
exit there. Hold on!

Alright, we are safely out now and have returned to our normal size. Just one more thing folks before we meet again in Chapter 9:

Adenoviruses end up killing virus-infected hepatocytes. Adenovirus is a "respiratory" virus, so it is out of it's element here in the liver. It acts like a raging bull in a fine china shop. The eventual destruction of the fine china can be predicted. The same is true of Adenovirus in liver cells. Recently Researchers have learned to breakup Adenovirus into a smaller Adenovirus - called a safe vector. Adenovirus has approximately 9,000 nucleotides. The newer "safer" vectors are approximately 7,000-8,000 nucleotides long due to the "deletion of the E-3 region of the virus". The E-3 region is like a gun in the Adenovirus' hand that is held to the big boss' head. It makes everyone work faster and harder. Recently, researchers have learned to beneficially use this safer "gun-less" adenovirus. Besides, it does have manners. Because of this safer "civil" Adenovirus, many great advances in medicine and modern genetics have been realized recently.
 

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