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Medical virology > Hepatitis B virus > Flashcards

Hepatitis B virus Flashcards

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USMLE® Step 1 flashcards
1
Q

Describe the disease burden of hepatitis B virus

A
  • one of the worlds most common and serious infectious diseases
  • > 50 of primary liver cancers occur in HBV carriers
  • 10th leading cause of death is HBV associated liver cancer
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2
Q

What serious diseases do 25% of HBV carriers develop?

A
  • hepatocellular carcinoma
  • cirrhosis
  • liver failure
  • chronic hepatitis
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3
Q

What are the major routes of HBV transmission?

A
  • blood
  • sexual
  • mother to infant
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4
Q

What kind of bodily fluids is HBV found in?

A
  • blood and wound excretions
  • lower amounts in saliva and semen
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5
Q

What is the structure of a HBV??

A
  • enveloped
  • dsDNA with one circular strand and one incomplete strand
  • core protein surrounds the genome
  • lipid envelope contains surface glycoproteins such as S
  • can produce subviral particles that act as decoys for antibody + complement binding
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6
Q

Describe the HBV genome

A
  • multiple reading frames encode for different proteins
  • 4 mRNAs encode them all
  • polymerase, core, surface glycoproteins and HBxAG involved in virus gene expression and replication
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7
Q

What does it mean that HBV has incomplete dsDNA?

A
  • negative strand has a fixed length that is longer than the genome and overlaps itself
  • the postitive strand is only 50-90% complete
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8
Q

How does HBV enter the cell and the nucleus?

A
  • binds low affinity receptors until it reaches a high affinity one and then enters by host mediated endocytosis
  • transported to the nucleus where the partial genome is repaired by host enzymes to form covalently closed circular DNA that associates with histomes and other proteins in the host chromatin
  • replicated and transcribed by host machinery
  • can exist as an episome in the nucleus
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9
Q

Why is it difficult to target the repaired, closed form of HBV?

A
  • so similar to host DNA
  • antivirals dont work
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10
Q

Why is the HBV genome important in cancer development?

A
  • integration is not essential for replication but can occur
  • causes genome instability
  • often integrates into genes involved in tumourigenesis
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11
Q

How is HBV replicated once in the host nucleus?

A
  • transcriptionof cccDNA by RNA polymerase II produces mRNA and pgRNA
  • pgRNA associates with polymerase and core protein to form a particle in which reverse transcription takes place
  • genome amplification can also occur
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12
Q

What about HBV reverse transcription is different to that of retroviruses for example?

A
  • retrovirus transcription occurs as the virus enters the cell
  • HBV reverse transcription into ssDNA occurs within the capsid
  • genomes are partially formed when the virus leaves the cell as it does so during reverse transcription
  • results in ssDNA with incomplete positive strand
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13
Q

What are the clinical features of childhood infection with hepatisis B?

A
  • 90% develop chronic infection
  • can then become non-replicative carriers or develop chronic hepatitis
  • 40% of those with chronic hepatitis will develop cirrhosis
  • 10% will have spontaneous clearance
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14
Q

What are the clinical features of adulthood infection with HBV?

A
  • only 5% develop chronic infection
  • can then become non-replicative carriers or develop chronic hepatitis
  • 15-20% will develop cirrhosis
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15
Q

What are some host factors associated with increased cancer risk in HBV carriers? (5)

A
  • male gender
  • younger age at primary infection
  • older age generally
  • presence of liver cirrhosis
  • diabetes and obestity
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16
Q

What are some viral factors associated with increased cancer risk in HBV carriers? (2)

A
  • persistently high viraemia
  • HBV genotype
17
Q

What are some environmental factors associated with increased cancer risk in HBV carriers? (2)

A
  • alcohol consumption
  • nutritional factors such as iron overload or dietry exposure to Alfotoxin B
18
Q

Describe the epidemiology of HBV

A
  • genotype C predominates asia and is most likely to cause cancer
  • certain countries are at higher risk then others possibly due to the presence of different genotypes
19
Q

How does HBV cause liver damage?

A
  • not directly cytopathic
  • hypothesised that damage is largely due to cellular recognition and destruction of infected cells similarly to in HCV
20
Q

Name 5 ways in which HBV contributes to HCC

A
  • insertional mutagenesis via integration of viral DNA into host chromsomes
  • viral HBx protein also increases genomic instablility
  • epigenetic modifications by HBx
  • modulation of cell death and proliferation pathways through prolonged expression of viral proteins such as HBx and envelope proteins
21
Q

What evidence do we have that HBV DNA integration increases cancer risk?

A
  • 80% of woodchuck HBV tumours show insertional Cmyc dysregulation
  • in humans HBV integration is seen more in tumour tissue than in normal tissue and insertion is frequently at sites that regulate pathways in cell signalling, proliferation and survival such as TERT and ROCK1
22
Q

What is the HBV HBVx protein?

A

an important transcription factor that binds the ccDNA to enhance its replictaion

23
Q

How can HBVx protein promote HCC development (4)

A
  • promotes and represses host TFs such as NFkB and ras
  • can activate apoptosis by interacting with mitochondrial proteins to activate caspases
  • can also repress apoptosis this way
  • can interact with histone modifying proteins to alter the epigenome
24
Q

Describe the antivirals available for HBV

A
  • suppress replication but cant eliminate the virus
  • use in those with life-threatening disease, who are immunosuppressed or are pregnant as vaccination doesn’t always protect from transmission to the baby
25
Q

What is the general mechanism of HBV antivirals?

A
  • nucleoside analogues that block viral replication
  • many target reverse transcription -> chain termination
  • but resistance is increasing
26
Q

What kinds of HBV vaccines are available?

A
  • inactivated vaccine made from the antigen particles of chronic carriers
  • recombinant empty particles made in yeast cells (reduce issues with using plasma/blood)
  • vaccines induce protective antiHBxAG in a 3 dose regime
  • some such as older, obese males may need more dosese
27
Q

How was HBV vaccination changed things?

A
  • decreases in infection worldwide
  • decreases in cases of liver cancer
28
Q

What are some problems with HBV vaccination?

A
  • 99% responsive in children but can be non-responsive in adults
  • up to 40% non-responsive in un-ideal situations i.e. old obese men
  • fails to protect against perinatal transmission 10-15% of the time
  • many chronic carriers don’t know they’re infected

Medical virology (15 decks)

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