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Chapter 18 Blog: Viral and Bacterial Genetics (Semon)

Page history last edited by Semon Rezchikov 13 years, 3 months ago

A.  Daily Blog

Viruses are non-living chemical particles that infect cells and force the cellular machinery to make more copies of themselves. They are tiny, viewable only with an electron microscope. They have a very simple structure: one or two copies of a minuscule DNA or RNA genome coding for pieces of the virus particle reside inside a protein covering called a capsid, which is then optionally enveloped by a lipid bilayer membrane. Capsids often have very regular, geometric shapes. Many capsids contain glycoproteins which are used to gain entry into the cell. Likewise, the enveloping bilayers often contain glycolipids. Bacteriophages (phages for short) are viruses that infect prokaryotic cells. They often have a more complex structure, with a polyhedral capsid attatched to a sort of "protein tail" and a "protein core" that allows the phage to inject its genome into a bacterium. All viruses and phages operate on essentially the same principle: inject genome into a cell; make the cell copy, transcribe, and/or translate the genome; allow the now built parts of the particle to self-assemble into a functional virus; exit the cell and cause more havoc.


AIDS is a disease that has recently been particularly prevalent in human populations. It is caused by a virus called HIV which destroys the immune system. Once the immune system is weakened, all sorts of diseases that would normally be easily fought off begin to invade the body, slowly destroying a person. HIV can produce no symptoms for decades, and can lie dormant for years (see the next paragraph). It has a single-stranded RNA genome. One of the things its genome codes for is reverse transcriptase, which can transcribe its genome into DNA for injection into the host cell genome or for amplification of the virus by RNA polymerase. To get into a cell, HIV, using a glycoprotein, first binds with a CD4 receptor (found on the surface of certain immune cells) and then with a CCR5 receptor, allowing entry into the cell. People with a mutation in their gene coding for CCR5 are immune to HIV! Numerous drugs targeting different aspects of HIV function have been developed to combat AIDS. For instance, because the HIV genome produces a single long polypeptide which must then be cleaved into smaller strands by a protease to create functional HIV, protease inhibitors have been developed as a treatment. Likewise, nucleoside analogs like AZT can screw up copying of the HIV genome. Molecules called chemokines can effectively bond with CCR5 receptors, competing with HIV and slowing the infection. However, because reverse transcriptase has a low fidelity, HIV acquires mutations rapidly and thus evolves a resistance against drugs very quickly, making it hard to treat. "Cocktails" of several drugs are often used to make it harder for HIV to acquire resistance.


Viruses (and phages) exhibit two basic types of infectious behavior: lytic and lysogenic. In the lysogenic cycle, the virus injects a copy of its genome into the host cell genome, so that the virus replicates every time the host cell replicates without actually damaging the cell. (This is how HIV stays dormant.) In the lytic cycle, the virus actively makes more copies of itself until the cell dies due to lack of resources or lyses due to a buildup of virus inside the cell wall. The virus can switch cycles depending on environmental conditions - for instance, if the cell is damaged or running out of nutrients, the virus can switch to the lytic cycle to increase its chance of finding a new, healthy cell.


Bacteria have a genome much different from eukaryotes. They only have one major "chromosome", which is circular and located in a central nucleoid region in the cell. The bacterial genome is organized using proteins completely different from the proteins that organize eukaryotic genomes. This large, central strand of DNA contains all the genetic material the bacterium needs to function. Bacteria also contain small loops of DNA called plasmids. Plasmids replicate independently of the genomic DNA and contain genes that may be useful, but not essential, to the bacterium's survival - namely genes for resistance to toxins, digestion of unusual substances, secretion of anti-bacterial proteins, development of virulence, and transfer of plasmids to other bacteria. 


Bacteria can transfer genes in several ways. Through a process called transformation, they can take in genetic material from their environment and incorporate it into their own genomes or store it as a plasmid. (This way if a bacterium dies other bacteria can acquire genes from it.) Bacteria that can undergo transformation are called competent. In transduction, viruses can take up a little bit of DNA from one bacterium and deposit it in another by way of infection. Finally, in conjugation, one cell extends a filament of plasma membrane to connect with another cell and transfer over DNA. This the bacterial equivalent of mating. Bacterial gene transfer allows bacteria to acquire resistance to antibiotics faster than the rate guaranteed by mutation. If one bacterium acquires resistance against an antibiotic, it can easily transfer it over to another bacterium, making it resistant as well! Without gene transfer, pharmaceuticals would make much less money because they would not have to constantly invent new drugs :-) 

B.  Useful Materials


I think that many of us don't really realize how small these buggers are. This is a fantastic animation showing the relative sizes of various small biological things.



Also, most of the pictures of viruses shown to us are simply cartoons depicting structure. Here are some actual electron micrographs of viruses. Dennis Kunkel is a wonderful man. (I've seen his images used in several lectures, and they are uniformly fantastic.) The images are effectively colorized to show glycolipid coats, capsids, etc.



This is a beautiful video of a virus infection:


XVIVO's biological videos are, in general, fantastic. Also, what Zirus Tech is doing is really cool.

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