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MIMM 324 > 33. Hepatitis B Virus > Flashcards

33. Hepatitis B Virus Flashcards

1
Q

3 main proteins in HBV

A
  1. HBsAg
  2. HBeAg
  3. HBcAg
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2
Q

2 forms of DNA in HBV

A
  1. cccDNA
  2. RC DNA
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3
Q

What does cccDNA stand for?

A

covalently closed circular DNA

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4
Q

what does RC DNA stand for?

A

relaxed circular DNA

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5
Q

how is HBV transmitted? (2)

A
  1. blood
  2. sexual
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6
Q

what type of virus is HBV?

A

orthohepadnavirus

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7
Q

genome of HBV

A

dsDNA with gaps

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8
Q

does HBV cause chronic infection?

A

yes

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9
Q

common incidence of transmission for HBV

A

vertical –> mother to child

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10
Q

baltimore classification

A

7

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11
Q

How many people are chronic HBV carriers? how many die of HBV per year?

A

248 million chronic HBV carriers

750,000 die of HBV per year

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12
Q

2 diseases that chronic HBV cause?

A
  1. liver cirrhosis
  2. hepatocellular carcinoma
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13
Q

4 stages in the course of chronic HBV infection

A
  1. immune tolerant
  2. immune clearance HBeAg-POSITIVE chronic hepatitis
  3. inactive carrier case
  4. reactivation HBeAg-NEGATIVE chronic hepatitis
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14
Q

what happens in stage 1: IMMUNOTOLERANT

A
  • high levels of eAg, sAg, DNA
  • low levels of liver enzymes

NO aggressive immune response/inflammation in liver

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15
Q

what happens in stage 2: immune clearance HBeAg-POSITIVE chronic hepatitis

A

eventually, immune system will take over
- high levels of eAg, liver enzymes
- fluctuations in HBV, sAg

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16
Q

what happens in stage 3: inactive carrier state

A

some ppl will lose eAg expression and develop anti-eAg antibodies
- due to mutation in core promoter during chronic replication in liver to prevent eAg expression
- but sAg and DNA are still produced

aka QUIESCENT

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17
Q

what happens in stage 4: reactivation eAg-NEGATIVE chronic hepatitis?

A

virus reactivated and enhanced
- DNA and sAg increase

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18
Q

which viral antigen is always present?

A

sAg

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19
Q

4 viral factors associated with HBV disease progression

A
  1. persistence of eAg
  2. persistenc of HBV DNA
  3. HBV genotype C, rather than genotype B
  4. core promoter mutation (loss of eAg)
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20
Q

4 environmental factors associated with HBC disease progression

A
  1. alcohol
  2. smoking
  3. aflatoxin
  4. HCV, HDV, HIV co-infection
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21
Q

5 host factors associated with HBV disease progression

A
  1. male
  2. old
  3. recurrent alanine aminotransferase
  4. cirrhosis
  5. diabetes
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22
Q

3 diff HBV particles? which is infectious?

A
  1. Dane particles –> infectious
  2. Filaments
  3. Spheres
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23
Q

why does HBV express large amounts of S antigen?

A

to exhaust the immune system and make it defective

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24
Q

why are there non-infectious HBV particles?

A

act as decoy to exhaust the immune system and make it defective

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25
Q

2 roles of cccDNA

A
  1. template for RNA pol II to make viral mRNA for viral proteins
  2. transcribed by RT to make RC DNA copies for packaging
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26
Q

2 receptors that HBV binds for entry

A
  1. NTCP
  2. EGFR
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27
Q

What does NTCP bind on the virus?

A

binds pre-S1 region on LARGE envelope proteins

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28
Q

what are the 3 envelope proteins? which type of particle has all 3?

A

large, middle, small

dane particles have all 3

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29
Q

why is there tropism for the liver?

A

NTCP is present only on hepatocytes for bilirubin export

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30
Q

what happens once infectious particles bind NTCP and EGFR? 5 steps

A
  1. capsid with RC DNA enters
  2. RC DNA transported to nucleus
  3. polymerases and ligases fill in the gaps to make cccDNA
  4. cccDNA makes subgenomic RNA and pregenomic RNA
  5. pregenomic RNA is recognized by RT to make RC DNA for packaging
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31
Q

what type of polymerase is RT?

A

DNA pol

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32
Q

describe the virion DNA

A

+ strand is incomplete, - strand is full

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33
Q

how many promoters?

A

4

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34
Q

how many terminators?

A

1

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35
Q

how many major RNA are produced?

36
Q

4 major RNA:

A
  1. C
  2. preS1
  3. preS2
  4. X
37
Q

what are the 2 subspecies of 3.5kb RNA transcripts

A
  1. precore-core
  2. pregenomic
38
Q

what does precore-core encode?

39
Q

is precore-core or pregenomic longer?

A

precore-core

40
Q

why is precore-core longer than pregenomic?

A

it has extra aa that allow for eAg secretion

41
Q

what does pregenomic encode?

A

core and pol

42
Q

how is pol translated preferentially over core in pregenomic RNA?

A

pol is downstream of core –> when ribosome binds, there is leaky scanning to allow pol translation

43
Q

what is expressed in the heterogenous 5’ UTR?

A

more S than pre-S2 is expressed

44
Q

what is produced if preS1, preS2, and S are all encoded?

A

large surface protein

45
Q

what is produced if preS2 and S are encoded?

A

middle surface protein

46
Q

what is produced if S is encoded?

A

small surface protein

47
Q

what do the 3 different versions of S give rise to?

A

these 3 versions of S that differ by length give rise to the different particles

48
Q

what antigens does the dane particle have?

A

large, middle, small

49
Q

what antigens do the filaments have?

A

middle and small

50
Q

what antigens do the spheres have?

51
Q

what 5 proteins are found in the virion?

A
  1. large surface protein
  2. middle surface protein
  3. small surface protein
  4. core protein
  5. polymerase
52
Q

describe the polymerase in the virion and how this affects its function

A

covalently linked to the genome –> has terminal protein that acts as primer

53
Q

what is found between the X and core?

A

regulatory elements

54
Q

4 regulatory elements between X and core

A
  1. polyA signal
  2. epsilon stem loop
  3. DR1
  4. DR2
55
Q

what is the polyA signal for?

A

once transcription is complete, polyA signal allows for RNA stability and translation regulation

56
Q

how is HBV RT similar to HIV (2)? how is it different (1)?

A

HBV RT is similar via polymerase and RNAse H activity

HBV RT is different bc has conserved tyrosine at terminal protein acting as primer

57
Q

what is found on the 5’ end of pregenomic RNA?

58
Q

describe the initiation and steps of RT (6 STEPS)

A
  1. RT recognizes unpaired bases at the epsilon loop
  2. with the tyrosine, it can add 3-4 nt as a primer
  3. this primer can base pair with DR1 on 3’ end –> 1st template switch
  4. RT makes first -DNA
  5. RNAse activity degrades the RNA template
  6. makes LINEAR dsDNA or RC DNA
59
Q

what does the linear dsDNA do?

A

not packaged in the virus –> can integrate into host

60
Q

how does linear dsDNA integrate into host? why is only S protein made?

A

chews off ends and integrate into chromosomes where there are chromosomal breaks

since the ends get degraded, the core promoter sequences are lost so only S is made

61
Q

where does the RC DNA go?

A

packaged in the capsid

62
Q

describe the things involved in RT initiation

A

RT, heat shock proteins, NTPs, energy, etc. to make priming complex

63
Q

after natural infection, what Ab are produced? what is the result

A

Ab against sAg (aka anti-HBs) which allow protective immunity

64
Q

what are current HBV vaccines?

A

injection of recombinant proteins derived from PreS/S region

65
Q

how can you prevent mother-child transmission?

A

anti-HBV immunoglobulin injection post-exposure

66
Q

what is a reason why HBV causes chronic infection?

A

once nucleocapsid is made, can be send back to nucleus to make MORE cccDNA –> cccDNA is very stable

67
Q

what was the first HBV vaccine derived from? what replaced this type of vaccine?

A

first was BLOOD-derived

then replaced by yeast-produced recombinant HBV vaccine

68
Q

how are HBV vaccine administered?

A

intramuscularly

69
Q

what is the common course of treatment for HBV vaccines?

A

usually 3 injections, 1-6 months apart

70
Q

what determines the number of HBV vaccine injections someone will get?

A

based on amount of anti-sAg

71
Q

2 types of non-vaccine HBV treatments

A
  1. IFN-alpha
  2. nucleoside/nucleotide analogs
72
Q

why is HBV not curable?

A

cccDNA is very stable!

73
Q

what is the only curable chronic hepatitis virus?

74
Q

what does HDV stand for?

A

hepatitis delta virus

75
Q

what is HDV considered to be?

A

sub-viral agent

76
Q

genome of HDV

A

circular negative ssRNA

77
Q

what does HDV depend on?

A

depends on HBV for replication

78
Q

describe the envelope proteins of HDV

A

HDV shares HBV envelope proteins

79
Q

3 things that HDV encodes for

A
  1. long delta antigens
  2. small delta antigens
  3. ribozymes
80
Q

what does it mean for HDV for encode ribozymes?

A

genome has enzymatic activity

81
Q

what does HDV undergo? by what enzyme?

A

HDV undergoes RNA editing by adenine deaminase

82
Q

3 RNA species involved in HDV

A
  1. circular -ssRNA genome
  2. circular +ssRNA antigenome
  3. linear mRNA
83
Q

how does HDV ribozyme work?

A

catalytic cytosine cleaves to expose 5’ guanosine

84
Q

which RNA has the ribozyme?

A

genomic and antigenomic RNA

85
Q

describe the production of HDV mRNA (3)

A
  1. host pol transcribes to linear
  2. ribozyme cleaves it to shorten it
  3. becomes mRNA that can make delta antigen

MIMM 324 (37 decks)

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