1c Viruses

What are the 3 main ways that viruses infect/enter cell?

-Bacteriophages inject their genetic material inside bacteria cell -Viruses bing to specific receptors on surface of the cell. This is called receptor mediated endocytosis -Envelop viruses use Direct fusion

Lets talk about specific retrovirus: HIV that enters the cell through direct fusion.

-First after the retrovirus enters the cell it must undergone process called UN-COATING where the protein coat is dissolved. This released ssRNA and the 3 proteins into the cytoplasm of the cell. -First protein that virus brought with it is reverse transcriptase that will reverse transcribe RNA forming complementary cDNA stand (remember that usually you take DNA and make into RNA). And then it will reverse transcribe a second cDNA so that that two cDNA will combine to create double stranded DNA. So in this step you are revers transcribe RNA→cDNA two times to create double stranded DNA. -Second protein that virus brought with it is called INTEGRACE and clips off 3' end on the double stranded cDNA. This forms the sticky ends and integrates the viral DNA into host genome. -The DNA that was integrated into host DNA does not have the repressor gene so it actively transcribe every time that host DNA is transcribed to mRNA. -mRNA exist the nucleus to cytoplasm and some of it is being translated into Capsid proteins and the 3 proteins that we began with. Other mRNA is self assemble into new viruses. Since you have almost all the parts needed for the new HIV virus -However these new viruses are missing envelope that is made out of lipids. The way how they will get the membrane envelope is bc they bud off the host cell taking some of the membrane with it. But they are still called IMMATURE viruses. How do they become mature? The last protein that virus brought with it is PROTEASE will cleave proteins to activated it.

Structure of virus: Note that this is just general idea.

-genetic material -protein coat→CAPSID -sometimes envelope that is made out of lipids and it surrounds capsid.

There are 4 things that dustings viruses from each other:

1) Size (viruses are super small. Bacteria 100 times larger then virus). Also, some viruses are bigger or smaller then others. 2) Shape: viruses have CAPSID that can have different shape and size. Each capsid is made of CAPSIOMERE protein. 3) Genetic information: they can contain one of the 4 options: double stranded DNA, single stranded DNA, double stranded RNA and single stranded RNA. 4) viruses are obligate intracellular parasite. So they must invade other cells. They way we distinguish viruses is by the type of host they invade. Viruses that invade bacteria are call bacteriophages, viruses that invade eukaryotic cells (humans) have famous names such as: poxvirus, harpies virus

Viruses have different ways to get into different cells? So they must adopt their shape to be able to get into the cell or inject nucleic acid into the host cell:

1) Viruses attack bacteria by injecting their nucleic acid inside the bacteria cell and leaving the protein coat outside. They adapted their shape by having TAIL FIBERS AND TAIL SHEATH. Tail Fibers attach to the bacteria and genetic material is injected through tail sheath. These are called COMPLEX VIRUSES. 2) Viruses can't inject genetic material to eukaryotic cell. They must sneak in the cell. Every cell has receptors on its surface viruses can take advantage of them and signal the receptor to take virus in. This is receptor mediated endocytosis. Some viruses contain envelopes that are made of phospholipid bilayer that will allow them to fuse in with membrane without using receptors. This gives virus extra advantage and easy entrance to the cell. This is called: DIRECT FUSION

How do viruses replicate? We are talking here about Bacteriophages.

Because viruses can't replicate by themselves the first thing they must do is: Get inside the cell. There are 3 ways that virus can get inside the cell. Receptor mediated endocytosis (non-envelope), direct fusion (envelop virus) or just injecting their nucleic acid inside the cell. Once the nucleic acid is inside the cell its ready to reproduce and take over the cell. But it makes a choice. It can take over the cell, make copies of itself and *self-assemble* which means that it will package itself in protein coat. Since the virus will be making more and more if itself the cell will not be able to hold all the viruses inside and it will lyse. These viruses that just have been release will be ready to infect nearby cells and spread through the whole organism. This will create the biggest amount of virus in shortest time. Or it can wait and just sit in the cell. Maybe there is no other cells or bacteria around to infect so there is no reason to kill the host. But in order to survive viral genetic material must combine with host genetic material. So that the host can't tell that the virus is inside the cell. The reason why the nucleic acid of virus is not expressed is bc there are *repressor genes* that repress that genetic material to be expressed. this stage is called PROVIRUS or PROPHAGE and it is in DORMANT or LATONIT STAGE. Each time bacteria replicate it will also replicate the viral genome since its combined. But if something happened like bacteria is expose to UV light that will weaken that repressor gene. In that case cell will try to fix UV damage to DNA and it will cut out that pice of DNA that just happen to be virus. This will activate the virus. So eventually it will lyse the cell.

What receptors does HIV bind to?

CCR5 on white blood cell. Some people lack these receptors which will make them immune to HIV :)

Viral Life Cycle: LYTIC CYCLE of Bacteriophages.

During lytic cycle bacteriophage makes max use of cell machinery in very short amount of time. Once the host cell is swollen with new viral progeny it will lyse and release viral progeny. They will most likely infect other cell.

Why is it hard to kill HIV?

HIV integrates its genome into host genome and this allows the virus to infect the cell over and over again-each time cell replicates it DNA. So the only way to kill HIV is to kill the cell (that way you are getting rid of viral DNA).

What is the function of reverse transcriptase?

It synthesizes DNA from ssRNA.

Special case: Retrovirus that does not fit into Lytic or Lysogenic cycle.

Lets first look what makes retrovirus a special case and different then other viruses. Retrovirus is enveloped single stranded RNA virus. Inside the envelope in carries 3 special proteins : reverse transcriptase, integrace, protease. Retroviruses can enter cell through receptor mediated endocytosis or direct fusion.

Effects of prions:

Prions have been held responsible for a number of degenerative brain diseases, including mad cow disease, Creutzfeldt-Jakob disease, fatal familial insomnia, kuru, and an unusual form of hereditary dementia known as Gertsmann-Straeussler-Scheinker disease.

What does it mean NON LIVING INFECTIOUS AGENTS?

Subvirus particles just as viruses are categorized as NON LIVING INFECTIOUS AGENTS. They are non-living since they are non cellular. All they have is protein coat and genetic material. They can't make ATP and can't divide. So they need a host.

How do Viroids reproduce?

The RNA that they have its know as catalytic RNA. Catalytic RNA means that it can make or brake covalent bonds. Because it can do that it can self cleave and create more viroids.

What are VIROIDS?

They are much smaller then viruses and they are plant pathogens that have very small circular single stranded RNA. However now we know that they also infect humans: hepatitis D virus.

What are SUBVIRAL PARTICLES?

They are smaller then viruses. They can be divided into 2 categories: VIROIDS AND PRIONS.

Why viruses are not living things?

They are super small, they are made out of protein coat and they contain nucleic acids. They can't make their own ATP since they don't have any mitochondria or membrane bound organelles. They also don't have DNA replication machinery so they can't replicate by themselves. So they must invade other living cells and use their replication machinery to live.

How do Viroids work?

They can bind to RNA and silence the genes. This will prevent synthesis of proteins and this can damage plant.

What are PRIONS? There were discover recently since scientist argued if proteins can be infectious by themselves.

They have no genetic material (No DNA or RNA). They are only made of proteins. Normally many proteins are made of α helixes. But prions are shaped in β confirmation. It is though that when β sheets come in contact with α helixes they "convert" α helixes into β sheets. They trigger misfiling of proteins. This conversion of protein to β sheets reduces protein solubility and cell is unable to degrade this protein. This creates proteins deposits that collect in brain.

Do not confuse VIROIDS with VIRIONS.

VIRIONS are whole viruses (protein coat + RNA) vs. Viroids are plant infectious agents.

Viral Life Cycle: PRODUCTIVE CYCLE

Virus will enter the cell, replicate and then leave the cell by fusing with cell plasma membrane in the process known as EXTRUSION. By doing this virus is not harming the cell and continue house the cell.

Viral Life Cycle: Lysogenic Cycle of Bacteriophage.

Virus will integrate its genetic material into host genome and every time bacteria replicate the virus replicates as well. However environmental factor such as UV, chemicals, light might cause the virus become activated and revert into Lytic cycle.

Notice how viruses will move DNA from one bacteria to another increasing DNA diversity

When viruses are self assemble in the cytoplasm of the cell some of the bacterial DNA can also be packed and moved to other cell when new bacteria is infected.

Can Lysogenic cycle be beneficial to bacteria?

Yes, since infection with one virus makes bacteria kind of resistant to infection to other virus-SUPERINFECTION (two or more viruses infect at the same time). And Lysogenic cycle of virus is kind of harmless to bacteria there might be some evolutionary advantages to this.