Inflammation and immunopathology- hepatitis virus

Question 1

Name the hepatitis strains in the hepatitis alphabet.

Answer 1

Hepatitis A, B, C, D and E exist.

Question 2

Which strain was the first to be discovered?

Answer 2

Hepatitis B.

Question 3

Which strain is the most infectious?

Answer 3

Hepatitis B. It is a pararetrovirus meaning that it has a DNA genome but an RNA intermediate. It is most infectious because one particle is enough to spread the virus.

Question 4

What are the 3 ways in which Hepatitis B can be transmitted?

Answer 4

1. Perinatal- mother to baby
2. Sexual
3. Parenteral- via injections or blood transfusions.

Question 5

Does hepatitis B have a high virion production?

Answer 5

Yes.

Question 6

Does hepatitis B have a high genetic mutational rate?

Answer 6

Yes.

Question 7

What is the consequnce for the hepatitis B virus having such a high genetic mutational rate?

Answer 7

The formation of quasispecies- quasispecies refers to there being different types of the Hepatitis B virus that have evolved to evade immune responses, vaccination and other antiviral drugs.

Question 8

Is the Hepatitis B genome big or small relative to other organisms?

Answer 8

It is super small.

Question 9

Does hepatitis B produce proteins?

Answer 9

Yes, it produces lots of viral proteins that are detected as antigens by the body and are responsible for inducing liver cancer.

Question 10

Describe the cellular mechanism in which the Hepatitis B virus uses to invade liver cells.

Answer 10

The hepatitis B virion produces a special protein called the Pre-S1 protein. This protein binds to a special receptor on the surface of the liver cell called the sodium taurocholate co-transporting polypeptide receptor (NCTP). This receptor is used normally for uptake of bile salts, metabolites and drugs.

Question 11

In hepatitis B viral replication, the RNA intermediate known as pgRNA is transcribed. What does this produce?

Answer 11

This results in minus strand DNA synthesis, which produces plus strand DNA synthesis which finally produces cccDNA. cccDNA remains in the nucleus and is incorporated into the host’s genome. Because of this hepatitis B once cleared can re-infect the host.

Question 12

Which hepatitis genotypes are the asian ones?

Answer 12

B and C genotypes.

Question 13

which hepatitis genotypes are the african ones?

Answer 13

E and A1 genotypes.

Question 14

What are hepatitis genotypes?

Answer 14

These are a class after the strain, so hepatitis B has multiple genotypes or versions of it around the world. Each genotype has distinct behaviour. Hepatitis B’s C genotype is more aggressive than B and D is more aggressive than A.

Question 15

What is a hepatitis subtype?

Answer 15

This is the next class after genotype, because even the genotypes have different versions.

Question 16

Which hepatitis subtype is associated with rapid progression to liver cancer in African males?

Answer 16

Subtype A1 of Hepatitis B genotype C.

Question 17

What is the mechanism in which the hepatitis B virus induces disease in its patients?

Answer 17

It is not the virus strain itself, but the immune system’s response to the virus that causes pathology. The pathological immune response is from the CD8+ cytotoxic t-cells.

Question 18

Describe the pathology progession in the liver than can be induced by these cytotoxic t-cells?

Answer 18

Hepatitis B first causes acute then chronic inflammation of the liver, which then progresses to cirrhosis of the liver and lastly liver cancer.

Question 19

What is the Hepatitis B antigen negative strain?

Answer 19

Antibodies had been produced by pharmaceutical companies against HBV antigens to clear the viral infection. However, the virus caught onto this and mutated itself so that it no longer produced the antigen. This strain is called the hepatitis B antigen negative strain.

Question 20

How does HBV induce liver cancer (HCC)?

Answer 20

This mechanism isn’t known. But the viral strains show more DNA splicing, which is incorporation of bits of the viral genome into the host’s genome. Increased splicing of viral DNA was evident in HCC.

Question 21

What are the 3 ways in which the HBV virus tries to make itself invincible, or chronic and persistent in the host?

Answer 21

1. HBV antigens

2. HBV cccDNA and minichromosome.

Question 22

Is HBV good at evading the host’s immune responses?

Answer 22

Yes. It’s really good at evading them.

Question 23

list the typical ways in which the adaptive immune system responds to an acute, self-limiting HBV infection?

Answer 23

1. vigorous CD4+ and T-helper response to HBe and HBc antigens.
2. vigorous CD8+ cytotoxic t-cell response to the infected hepatocytes.
3. The Th1 cell lysis via apoptosis pathway is dominant

Question 24

list the typical ways in which the adaptive immune system responds to an chronic HBV infection?

Answer 24

1. weak CD4+ response to the HBe and HBc antigens.
2. Secretion of antibodies to clear the HBV antigens
3. Th2 response is dominant (antibody formation)