DERS 05 - GIT Infections 2 Flashcards
Answer the following about hepatitis B virus (HBV):
- Enveloped?
- Shape?
- Genome type?
- Stability?
- Structure?
- Enveloped, spherical, with a partial dsDNA genome
- Stable at low pH, freezing temps, and in the presence of detergents and moderate heat
- Envelop contains 3 glycoproteins/surface antigens: S, M, L
- Inner nucleocapsid containg genome and viral Polymerase
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What is HBV’s primary method for evading the immune system?
The majority of the viral proteins produced aren’t used for making virions. Instead, they are released as is, vastly outnumbering the virions and acting as decoys
Describe the unique genome of HBV and the proteins coded by it
It only codes for 4 mRNAs and 1 full-length pre-genomic RNA. The 4 mRNAs code for many proteins by use of different ORFs:
- ORF P - viral polymerase - has DNApol, RT, & RNase H activity
- ORF S - HBV surface proteins - HBsAG (S,M,L), and Pre-S (viral attachment)
- ORF C - HBcAG (nucleocapsid protein) and HBeAG (unknown function)
- ORF X - HBx protein - transactivator that helps establish in vivo infection
Detail the HBV life cycle
- Pre-S proteins attach to hepatocytes for endocytosis
- After endocytosis, membrane fusion occurs, releasing the nucleocapsid, which enters the nucleus
- Host DNApol converts the viral partial dsDNA into complete dsDNA, called cccDNA (covalently closed circular)
- Host DNApols the 4 mRNAs and 1 pre-genomic RNA
- Host machinery makes viral particles which self-assemble
- HBcAg forms capsid
- S, M, and L proteins (HBsAG) form envelope
- vPol uses its RT activity and the pre-genomic RNA to make one negative sense cDNA
- vPol RNase H activity degrades the pre-genomic RNA
- vPol DNApol activity partially copies the negative sense cDNA, making the complete partial dsDNA viral genome
Facts to know about HBV epidemiology
- HBV is worldwide
- It is classified into 8 genotypes (A-H) and subgenotypes which are prevelant in different parts of the world and require different treatment
Facts to know about HBV transmission
Extremely infective - one virion is enough to establish infection
Transmission is via blood or unportected sex
Are hepatitis B infections acute or chronic? Which populations to affect the most? What can an HBV infection lead to?
Both
- Acute (<6mo) infections typically affect adults
- Acute infections almost always resolve
- Fulminant hepatitis can develop, which is fatal
- Chronic infections typically affect infants and is usually contracted from the mother during birth (vertical transmission). Chronic infections can develop several ways:
- Asymptomatic
- Chronic persistent
- Chronic active - develops into liver failure, cirrhosis, and hepatocellular carcinoma.
What are the clinical features of an acute HBV infection
- Fever, rash, and arthritis is sometimes seen before any other symptoms
- Typically preicteric and icteric symptoms
Describe the pathogenesis of HBV
- HBV does its thing within the cell
- MHC-I present viral antigens which CD8+ T cells recognize, resulting in them doing two primary things
- Kill the HBV infected cell
- Initiate nonspecific inflammatory response by releasing TNFα and Interferon gamma
- This all causes disruptions in cell signaling and destruction of p53, which leads to more cell necrosis and possibly clonal expansion of a particular cell type, resulting in hepatocellular carcinoma.
Describe how HBV is diagnosed
- Qualitative and quantitative detection of the viral antigens HBsAG, HbeAG, and HBcAG; and of antibodies against HBs an HBc
- This is done using various immunoassays and qRT-PCR
- Blood work for ALT/AST/LDH/AP to measure extent of liver injury
- Liver biopsy
What is the HBV window period and why is it important?
During an HBV infection, there is an abundance of HBsAG (the decoy particles). Because of this, the few Anti-HBs particles made become complexed with a lot of HBsAG, making it undetectable. There is a window period, during convalescence, where the HBsAg levels have fallen to the point where neither they nor the anti-HBs particles are detectable (because of the complexing)
This is important because while a positive HBsAg indicates infection, a negative result may be a FN. Therefore, the IgM anti-HBc is tested for to determine the presence of an acute infection (which is when the window period would be)
Write out the test result for the following in a HBV susceptible, immune due to natural infection, immune due to HB vaccine, acutely infected, and chronically infected individual:
- HBsAg
- anti-HBc
- IgM anti-HBc
- anti-HBs
Facts to know about HBV treatment and prevention
- Prevention
- Subunit vaccines
- Immune globulin given after infection but before Sx
- Screening blood supply
- Eliminate risky behavior
- Treatment
- Interferon and/or
- Antivirals-polymerase inhibitors (nucleoside/nucleotide analogs)
What kind of genome does HDV have? List the proteins it has and what they’re used for.
- -ve sense ssRNA in a rod shape due to extensive base pairing
- HDV utilizes HBsAG proteins for its evelope, which means HDV infections cannot occur with HBV coinfection or chronic infection
- HDV nucleocapsid proteins are:
- small delta antigen (S-HDAg), which helps control genome replication
- large delta antigen (L-HDAg), which is required for virion assembly
Describe the HDV life cycle in the level of detail we need to know.
- HDV binds to hepatocyte receptor and is endocytosed
- HDV is uncoated in the cytoplasm and the genome is translocated in the nucleus
- Host RNApol 1 and 2 produce the +ve and -ve sense viral RNA
- +ve sense strand is used to make the HDV viral antigens
- The -ve sense strand complexes with the HDV viral antigens and moves into the cytoplasm
- Virion production is complete when HBsAg particles form an envelope around the HDV capsid
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