Lec 19 - Bloodborne viral infections 1: HBV and HCV

Question 1

What are the main concerns associated with hepatitis viruses?

Answer 1

• Cause hepatitis and liver cancer with a bad prognosis
• High risk of occupational exposure due to blood exposure and extensive survival on fomites

Question 2

Describe hepatitis viruses types A-G by transmission and result of infection.

Answer 2

A = enteral transmission and causes acute hepatitis
B = bloodborne/parenteral transmission and causes hepatocellular carcinoma
C = bloodborne/parenteral transmission and causes hepatocellular carcinoma
D = parenteral transmission; satellite virus; chronic infection when coinfection with B
E = enteral transmission and causes acute hepatitis
F and G = unknown significance

Question 3

Describe the Baltimore classification and T value of hepatitis viruses.

Answer 3

Group 7 = dsDNA circular genome with RNA section, 4 overlapping ORFs, and RNA intermediate, T = 4

Question 4

What are the 4 proteins of hepatitis viruses?

Answer 4

1. S = surface protein HBsAg
2. C = structural core protein HBcAg
3. P = non-structural precore protein/secreted e antigen HBeAg and polymerase
4. X protein

Question 5

Describe the life cycle of HBV.

Answer 5

1. Attachment to heparin sulfate proteoglycan with low affinity and NTCP transmembrane receptor (high affinity)
2. Clathrin mediated endocytosis
3. Uncoating and nuclear entry as relaxed circular DNA (RC-DNA) converted to cccDNA
4. Transcription by host RNA polymerase to pgRNA and sgRNA
5. pgRNA packaged with P protein into nucleocapsid and reverse transcribed
6. (+) DNA synthesised from (-) DNA strand to make RC-DNA

Question 6

What is the reason for the short RNA section in HBV’s genome?

Answer 6

Run out of nucleotides in nucleocapsid when pgRNA reverse transcribed by viral polymerase

Question 7

What is the function of HBV’s subviral particles (SVPs)? Describe their structure and list the 3 types.

Answer 7

• Divert neutralising antibodies
• Have envelope glycoproteins and host lipids in their structure but no genome
  1. Spherical SVP
  2. Filamentous SVP
  3. Dane particles

Question 8

Describe the transmission of HBV and list examples of how it can occur. What body secretions have the most virus?

Answer 8

• Parenteral transmission eg transplants, transfusions, needles, vertical, intra-familial, sex
• Most virus in blood and wound exudates, less in genital secretions and saliva, undetectable in sweat, milk and urine

Question 9

What Australian population/s has the most and least HBV?

Answer 9

• Endemic in Aboriginal and Torres Strait Islander populations especially in NT
• Very low in Tasmania from vaccination rates

Question 10

What is the incubation time for HBV? List some symptoms.

Answer 10

Incubation = 45-180 days
Symptoms = flu-like, icterus/jaundice, pruritus/itching

Question 11

What are the 3 types of disease resulting from HBV?

Answer 11

1. Acute = asymptomatic and cleared by host
2. Chronic = virus replicates for 6+ months after infection in 10% of cases
3. Fulminant = 1/1000 patients die in 10 days from immune destruction of hepatocytes

Question 12

Who is most at risk of chronic HBV infection? How is it prevented?

Answer 12

Pregnant women and young children at risk. Immunoglobins and vaccinations to infants within 12hrs of birth are administered

Question 13

How can you tell the difference between recovery of HBV and chronic infection/carrier? How is HBV exposure determined?

Answer 13

Clearance = anti-HBs and/or anti-HBe
Chronic/carrier = HBsAg and high ALT with no antiHBs and/or anti-HBe
Exposure = anti-HBc

Question 14

What are the treatment options for HBV?

Answer 14

• Nucleoside/nucleotide analogues eg lamivudine to inhibit viral DNA rep and reduce hepatic necrosis and conversion of S antigen to HBeAg
• Antiretrovirals for drug resistant virus

Question 15

What is the sign of active HBV replication?

Answer 15

HBeAg

Question 16

Describe the structure and genome of HDV.

Answer 16

Enveloped circular (-) ssRNA genome, large and small delta antigens, S and M glycoproteins

Question 17

What are the 2 types of HDV infection with HBV? How is it prevented?

Answer 17

1. Coinfection = severe HBV acute infection
2. Superinfection = chronic HBV carriers with HDV infection get severe chronic HBV infection
   Prevention by HBV immunisation

Question 18

What disease does HDV infection alone cause?

Answer 18

Asymptomatic or fulminant hepatitis

Question 19

What disease does HCV cause and why is it less dangerous than HBV?

Answer 19

Causes liver cirrhosis and liver carcinoma but treatment cures 95% of HCV

Question 20

Describe the structure of HCV virus particles in blood that allows them to enter hepatocytes.

Answer 20

Spherical hybrid/heterogenous lipoviral particles

Question 21

What are the 2 most common subtypes of HCV in Australia?

Answer 21

G1 and 3 from drug injections

Question 22

Describe the genome and structure of HCV and how it enters cells.

Answer 22

(+) ssRNA genome, single ORF, transcription and translation functions, RdRp
Clathrin mediated endocytosis

Question 23

How do HCV proteins change the structure of host cells?

Answer 23

Viral proteins interact with host factors to rearrange intracellular membranes of ER = membranous web microenvironment

Question 24

How is HCV transmitted and what are the different disease progressions after what incubation time?

Answer 24

• Parenteral transmission with blood contact and sexual transmission most common
• 2-6 month incubation
• 80% asymptomatic
• 70% of infections become chronic persistent with cirrhosis in 10-20%