8. Cancer Human Viruses Flashcards
NOTE:
Cancer viruses are also called:
____ viruses and ____ viruses
These names are interchangeable.
oncogenic
tumorigenic
A general example of how viruses can cause cancer
Number 1/2/3 are saying that a virus can infect. On the top in number 4 its saying they can cause tumors. Make the separation into the two parts: tumor and infection. Some but not all can cause tumors.
1. Lytic infection
A. The virus goes in and ____ the cell.
2. Persistant infection
A. Some viruses go in and they reside there at ____ levels. They are held down by the immune system and don’t explode unless you become ____.
3. Latent infection
A. Like ____. Go into the genome and stays there. There are some other tricks too for latency.
- Tumor
A. ____ is the first step towards cancer. It doesn’t mean that you have cancer yet. It
just means that you took a cell that is now able to live forever.
B. In contrast, if you took any cell from your body and culture it they will only Iive for so many
cell cycles.
C. Immortalized cells are not necessarily ____ because if you put one into an organism
the immune system may detect and kill it. To become a tumor the ____ response must
be evaded.
D. Viruses don’t “want” to cause ____. A small subset of the ____
used for lytic infection can inadvertently be used to make a cell become ____ and
eventually become a tumor.
destroys
low
immunodeficient
HIV
immortialization
cancerous
immune
tumors
machinery
immortalized
Cancer viruses immortalize cells as a first step in tumorigenesis
Normal cells will grow and completely stop growing due to contact inhibition of adjacent cells –> virus –> cells become virally transformed are not ____ by adjacent cells. they continue to divide. they are immortalized.
Cancer viruses immortalizing cells is our first step in tumorigenesis.
• Take cells from human and put them on a tissue culture plate. There’s 4 normal cells with nuclei (left picture).
• If you take a virus and you infect the cells – you either kill all of the cells or depending on if you put in the cancer genes only for this virus – In some cases, you end up with ____ cells. This is basically all of these cells going crazy and forming a mass (right picture).
contact inihibited
immortalized
How do viruses disrupt the cell cycle and how does this lead to cancer? Part I
- human body has 10^13 - 10^14 cells.
- the vast majority of these cells are non-dividing and have an arrested cell cycle, i.e., they are ____
Reads slide. Quiescent doesn’t mean they are sleeping. It means they are not ____. They are working, metabolizing, etc. We do have some rapidly dividing cells like our ____, blood cells. NON fast dividing cells would be ____ and neuronal cells.
quiescent
dividing
skin
muscle cells
How do viruses disrupt the cell cycle and how does this lead to cancer? Part 2
NORMAL CELL CYCLE: The pRB Check Points
When the rb protein becomes dephosphorylated (Rb) it binds to ____, which prevents E2F from ____ the cell cycle
NOTE: normal ____ cells remain at this stage
When the Rb proteins becomes phophosrylated, it dissociates from E2F, which now enables E2F to ____ the cell cycle
He wants to make the cell cycle simple. Remember two things: the gas pedal and the brake.
• Every cell has a cycle by nature. A cell has to go through a phase of which it is going to grow… like G is growth phase.
• A stage called S where there is DNA synthesis occurring. You have your genome and you are making a duplicate of it.
• And then you have M, which is mitosis where the cell has two copies of DNA and is going to divide and give you two cells. There are points where it stops (go to the next slide).
E2F
activating
quiescent
activate
How do viruses disrupt the cell cycle and how does this lead to cancer? Part 3
- when a virus infects a quiescent cell, it must ‘activate’ it in order to utilize the host cell machinery.
a viral protein causes loss of control of ____ checkpoints. the cell is no longer regulated and keeps dividing.
the cancer virus onco-protein (i.e. HPV ____) blocks control of cell cycle by binding RB. this enables the free E2F to go unchecked and stimulate the cell cycle continuously.
- Point is that in the cell cycle E2F is the gas pedal. It is a cellular gene/protein. It says GO.
- Then there is another protein called Rb that says STOP.
- When a virus infects a quiescent cell it must activate it in order to utilize the host machinery. What happens with cancer is that you are taking away the break. The cell should want to stop and it doesn’t. A virus protein causes loss of control of pRb checkpoints.
- There’s two famous proteins in science that you will read about forever in your career. One is a RB–retinoblastoma protein. The other is p53, which is the guardian of the genome.
pRB
E7
How do viruses disrupt the cell cycle and how does this lead to cancer? part 4
rapidly dividing cells, with no cell cycle check points, will accumulate mutations in their DNA. normally, cellularl ____ protein (the guardian of the genome) senses these mutations and either blocks the cell cycle or forces the cell to self-destruct (apoptosis).
p53
how do viruses disrupt the cell cycle and how does this lead to cancer? part 5
in virus infected cells, a viral (i.e. ____ protein of HPV) binds p53 cellular and prevents it from blocking the cell cycle or undergoing apoptosis
the cell is now ____ by the virus!
E6
immortalized
how do viruses disrupt the cell cycle and how does this lead to cancer? part 6
a continuous cell cycle generates mutations that ____ the genome and brings about cellular changes i.e. the ability to escape an ____ response. this progresses to tumor formation and ____
de-stabilize
immune
metastasis
introduction summary: how cancer viruses disrupt the cell cycle and cause tumors.
viral onco-proteins can disrupt the cell cycle (____) so that the cells continue to divide. by analogy to a car, the ____ is pushed all the way down.
the cell senses danger (DNA damage) but ____ and ____ are blocked (p53). the brakes don’t work. mutations lead to genome ____ which progress to tumors.
pRB accelerator growth arrest apoptosis destabilization
• Hepatitis B/C are big in the wheel representing all of the viruses. Very important. ____ is the predominant one. B has a ____, but C has a new ____. They are easily transmitted by ____.
C
vaccine
drug
blood
• What causes hepatitis?
The liver is the chemical factory of the body. It is where you process everything, especially foreign stuff. Every time you take a medicine, the medicine always goes through your liver first in something called ____
metabolism.
• Then it goes through it again, which is ____ metabolism.
• Each time you get modifications of the drug that was put in until it is destroyed and goes to the ____ and is excreted.
• If you get abnormal metabolism, and something is going wrong with the liver, the liver can give you hepatitis. This means ____ of the liver. If you OD on
Tylenol its because the liver is overwhelmed.
• If any of these insults (hepatitis B/C viruses, abnormality in metabolism), then you get inflammation of the liver. You eventually get ____, which is scarring and loss of function. And then eventually you get ____.
first pass
second pass
kidney
inflammation
cirrhosis
liver cancer
• Theres a lot of “hepatitis” viruses but they have nothing really in common other than the fact that they infect the liver. B/C are totally different viruses! One is ____ the other is ____.
• There is a vaccine for ____ (and for B but he didn’t say that here). There’s B/C which
are important for us. Then there’s the others.
RNA
DNA
A
hepatitis is defined as “liver inflammation”
what is viral hepatitis?
hepatitis means ____ of the liver. it is often caused by a ____ and most common forms are A, B and C.
liver disease caused by viral hepatitis ____ can progress to cancer.
Hepatitis is inflammation of the liver. It can be caused by many things but we are
looking at the B/C viruses. These (A/B/C) are the common viruses of the liver. None of them mean you will get liver cancer, it just makes it more likely.
inflammation
virus
B and C
How do you get liver cancer: • Drink tons of \_\_\_\_ • Hep B/C viruses ◦ \_\_\_\_ is the big one • When you drink alcohol and have hepatitis C it adds to the odds and the wheel grows. Its an \_\_\_\_ effect.
alcohol
C
additive
hepatitis
A - found in ____ water or food. ____ is available that gives lifetime immunity.
B - is ____. transmitted by ____ contact with bodily fluids. can cause chronic hepatitis, lead to cirrhosis and liver cancer. also has a ____.
C - is the most common ____ illness in the US. there is no ____ and it is transmitted in the same way as hepatitis ____. it also leads to liver failure and cancer.
new drug for hepatitis C (____)
unsanitary
vaccine
everywhere
direct
vaccine
blood-born
vaccine
B
epclusa
• Don’t get lost in this
• Modes of transmission of B/C - any kind of activity that causes a breakage of ____ and a fluid to fluid (____) exchange is how it works.
• Dental treatment with ____ equipment is a great way to transfer the
viruses.
blood vessels
blood-to-blood
unsterilized
Pathology of viral hepatitis
note: although hepatitis type B is a ____ virus and hepatitis type C is an ____ virus, their pathologies are very similar.
• Its a ____ cancer. Its not like you have a normal liver and then the next day its cancerous. Thats what this is showing.
• These viruses can cause progression to liver damage and they undergo a pathology that is common.
◦ First thing you see if ____ of the liver.
◦ Then you see ____ tissue.
◦ Then then you see ____ where liver is destroyed. This can lead to death.
You can’t process and get rid of things like medicine and foreign things now.
• Can take years
DNA
RNA
progressive
fibrosis
cirrhotic
liver cancer
- “What I would look at is the liver cirrhosis and the scar tissue to give yourself a background feel about what this is about.”
- (Start with blue circle). Shows how you can have any of the viruses and alcohol or compounds to injure the liver. It becomes a chronic disease. You get cirrhosis which is ____ (in red). These show you the certain cellular events that are occurring (subsequent pathways). So you go from well differentiated cells to ones that are poorly differentiated (purple). They are no longer functioning liver cells anymore.
- stellate cells are ____ storing cells
- cirrhosis is the replacement of normal functional liver cells with ____ tissue
- ____ nodules result from an increase in the amount of tissue that results from cell proliferation
- dysplastic nodules are abnormal appearing ____ cells
- ____ are structures at the end of chromosomes that protect them from fusion and degradation
scar tissue fat scar hyperplastic precancerous telomeres
• The numbers are not important and should not be memorized and will not be on the exam. But what you want to know for yourself is the magnitude of some
things.
• Even if you don’t die from a liver disease your ____ of life would be greatly
impaired. Can get cancer of the liver and that could kill you.
quality
hep B virus symptoms
- ____
- loss of appetite
- ____
- vomiting
- ____ & eyes (jaundice)
- dark-colored urine
- ____ stool
it is estimated that ____% f all americans have been infected with HBV
lethargy
fever
yellow skin
light colored
hepatitis type B virus transmission rates
• Mom can pass it to infant \_\_\_\_ • Can also be \_\_\_\_ ◦ \_\_\_\_ drug use, sharing needles ◦ Don't share \_\_\_\_ there's bleeding ◦ \_\_\_\_ contact ◦ Easy to transmit which is why its rampant
easily host to host IV toothbrushes sexual
note: ____ intergrates into the genome. ____ does not integrate.
• HBV DNA has these proteins. You can have a normal liver become a chronic hepatitis and a carcinoma. These show you the events the occur though every one of these kinds of relationships.
• When you have these events occurring. When you have the integration of HBV into DNA you get expression of these viral proteins that lead to the ____
inflammation of the liver, ____, and genetic instability.
• Genetic alterations and mutations are occurring and thats the bad part which will lead to the carcinoma/cancer.
hep B
hep C
necrosis
oxidative stress
possible outcomes of HBV infection
• Don’t memorize the stats just be aware of them.
• There’s ____ hep B infection. This leads to ____ HBV infection. This leads to chronic hepatitis.
• This is good at showing the timeline.
◦ ____% of people 5 years later end up with chronic hepatitis after getting
infected. Then 5 years later ____% end up with liver failure which can lead to
death. This is why we have so many people who need liver transplants.
- In 5 years 6-15% of people get ____ carcinoma which leads to death.
- The point is that something that occurred years before ends up causing problems ____ later.
acute
chronic
12-25
20-23
hepatocellular
years
hepatitis B vaccination
recombinant DNA vaccine
- introduced in 1986 in USA
- has replaced ____ vaccine
- ____ effective
- available as ____ or combined vaccine
active substance:
- HBsAg derived from culture of ____ or ____ cells
adjuvant:
- ____ or thiomersal
storage:
- ____
- ____ avoided
• HBsAg = Hep B surface antigen
◦ Viral protein that was through recombent DNA made in cells, either yeast or mammalian cells. Can be easily cultured in lab. Just the ____ part not the
viral part.
• Then you put it into an adjuvant that helps it to be delivered.
• Then you can freeze it and take it out and use it.
• Produced in 1986
plasma derived
cost
monovalent
yeast
mammalian
alum
2 to 8
freezing
protein
