Fenger (Hepatitis Viruses) Flashcards
What the 2 liver enzymes present in the serum that indicates liver disease?
Why?
AST: Serum Aspartate Aminotransferase
ALT: Serum Alanine Aminotransferase
Bc they are usually intracellular so there must be lysis of the cell so that these enzymes leak in to the serum.
What Hepatitis viruses are transmitted via blood?
Hep B, C, D
What Hepatitis viruses are transmitted by fecal-oral route?
Hep A, E
What Hepatitis virus belongs to the Picornaviridae family (+ SS RNA)?
Hep A
What Hepatitis virus belongs to the Flaviviridae Family (+SS RNA, enveloped)?
Hepatitis C
What Hepatitis virus is an enveloped, Partially DS DNA?
Hepatitis B (Hepadnaviridae family)
What Hepatitis Virus is Circular, Enveloped Negative SS RNA?
Hepatitis D
Name 3 DS DNA Viruses that belong to the Herpetoviridae Family that have the clinical feature of Hepatitis?
What newborn virus (+RNA)?
- EBV
- CMB
- HSV
Rubella (newborns)
Which Hepatitis?
- Picornaviridae
- Enterovirus Type 72
+ SS RNA
-very resistant, acid-stable, naked
Hep A
Which Hepatitis?
- *CLINICAL: low mortality**
- sporadic outbreaks
- short incubation
- NO CARRIER/CHRONIC STATE
Kids have milder disease than adults (like EBV, Polio)
-fecal-oral transmission by contaminated food and water
Vaccine candidates: homosexual men, IV Drug users, international travelers.
Hep A
True or False?
Viremia is established with the Hepatitis viruses.
True.
1o multiplication in GI tract epithelium and lymph nodes—->viremia-—>liver, kidney, spleen—-> virus in feces, urine, blood in preicteric (pre-jaundice).
Which Hepatitis?
- Immune electron microscopy detects virus
- ELEVATED Anti HAV IgM
-Long Term Immunity, but will not protect against the other Hep viruses
Hep A
What are the options for Prevention and Control of Hepatitis A?
1.
2.
- Kids - ?
4.
- Pooled Gamma Globulin (given 1-2 weeks post exposure)
- Inactivated/Killed Vaccine
- Kids: 2 immunizations (1st: 12 months, 2nd: 6 months later)
- HepA and HepB Combo - Twinrix, 4 doses
What is the name of the particle that is the ONLY infectious virus particle of Hepatitis B?
Dane particles
True or False.
Noninfectious particles are also found in serum of infected individuals.
True.
22 nm particle (HBsAg aggregates)
27 nm particle (core antigen aggregates)
*********What are the 3 particles found in the serum of a patient with Hepatitis B virus?
***********
- Dane particles - infectious particle
- HBsAg aggregates - noninfectious
3 Core Antigen aggregates - noninfectious
What is found within the core structure (HBcAg) of the Hep B Virus?
1.
2.
- Partial DS DNA (viral genome)
- Polymerase (reverse transcriptase) complex
Name the 3 Antigens of Hepatitis B Virus
HBsAg: ___________
HBcAg: ___________
HBeAg: ___________
HBsAg: surface antigen
HBcAg: core structure antigen
HBeAg: infectivity antigen
What is the Hep B antigen that you want in a vaccine?
HBsAg - elicits antibody response (neutralizing antibodies)
What HBsAg complex antigen is common with asymptomatic carriers?
What HBsAg complex antigen is associated with dialysis and drug addicts?
adw
ayw
Which Hep B antigen is the “infectivity” antigen?
It’s presence in the serum indicates that infectious virus is present in the patient.
HBeAg (derived from HBcAg)
Fact: Hepatitis B Virus Replication
2 Stages of Entry: Viropexis + Fusion
DNA Polymerase fills in the gap for partial DNA viral genome
mRNA release from the nucleus has 2 fates:
(1) Transcription by reverse transcriptase in to viral DNA genome
(2) Translation in to viral proteins
Definition: phagocytic engulfment.
viropexis
What makes up the Hep B Polymerase Complex?
1.
2.
3.
- DNA Polymerase (linked to full length DNA strand)
- Reverse Transcriptase
- Rnase H
Which Hepatitis B Polymerase complex enzyme?
function: copies DNA template into a complementary strand, converts partially double stranded DNA into double stranded DNA
DS DNA Genome is transcribed into viral RNA.
DNA polymerase
Which Hepatitis B Polymerase complex enzyme?
Function: copies an RNA template into a strand of DNA; therefore a DNA-RNA is formed.
Reverse Transcriptase
Which Hepatitis B Polymerase complex enzyme?
Function: specifically degrades the RNA strand of the DNA-RNA hybrid
RNase H
Where does replication occur for Hep B Virus?
nucleus and cytoplasm*
*******Hep B Viral RNA serves 2 purposes in the cytoplasm:
1.
2.
- Acts as messenger (mRNA), translated into proteins
- Serves as template for viral genome DNA synthesis
Hepatitis B Virus
Viral _______________ (enzyme) copies the full length strand of DNA to form the new genome (partially DS DNA).
DNA polymerase
The _______ (+ or -) DNA strand serves as the template for transcription of mRNAs that are then translated into viral proteins, structural proteins and polymerase complex.
negative DNA strand
True or False.
All Hep B Virus infections are acute. They do not progress to chronic infection.
False!
Most cases resolve, but some progress to a persistent disease or a chronic active disease.
Fact: Causes of Hepatitis B Vaccine.
- Blood Transfusions
- IV Drug Users
- Homosexual Men
- HBV Carriers
- Infants born to HBV infected moms
- Developmentally disabled
- Hemodialysis patients
- endemic HBV locations
Which one is more severe?
Liver biopsy:
HBsAg found in cytoplasm or HBcAg found in nucleus?
HBcAg in nucleus more severe liver damage.
What antibody indicates recovery from a Hepatitis B Virus infection?
Anti-HBs (anti-HB surface Ab)
What is the state of an HBV infection if Lab Results come back as follows:
HBsAg +
HBeAg -
HBcAB (IgG)
Persistant, Asymptomatic Hep B
What is the state of an HBV infection if Lab Results come back as follows:
HBsAg +
HBeAg +
HBcAB (IgG)
Chronic Active Infection
Hepatitis B Virus Infection.
Antibody to _________ (what antigen) first (Ig____ followed by Ig____), then __________ antibodies develop in resolved cases, but IgG directed against HBsAg is not made in chronic active or persistent carriers
HBcAg
IgM then IgG
HBsAg
What are the options for Prevention and Control of Hepatitis B?
- For Neonates (IM) born to infected mothers?
- If person allergic to yeast proteins, given to pregnant women
- HBsAg produced in yeast (not glycosylated), very effective
- What perservative (mercury based) was removed from vaccination prepartion?
- Combines Haemophilus influenza type B and Hep B vaccines
- Hyperimmune HBIG given IM + vaccine ASAP
- Heptavax
- Recombivax, Engerix B
- Thimerosal
- Comvax
Fact/FYI: Chronic Hepatitis B does require one of 7 drug treatments approved in the USA.
-Injectable interferon alpha
-Pegylated Interferon*
- Oral nucleoside analogue, Lamivudine
- Nucleotide analogue, Adefovir
-Nucleotide analogue, Enticavir*
-Nucleotide analogue, Telbivudine
-Nucleotide analogue, Tenofovir*
* First line drug treatments
HBV carriers have 200x greater risk of primary __________ (cancer) than uninfected individuals.
Primary Hepatocellular Carcinoma (PHC, HCC)
Name 3 Possible Mechanisms for Primary Hepatocellular Carcinoma.
1.
2.
3.
- HBV DNA has a gene (HBx) which produces a transcription activation factor which not only activates viral genes, but also turns on cellular genes (oncogenes)
2. integration of HBV genome into cell DNA they are juxtaposed next to a protooncogene
3. initiation of liver necrosis by HBV infection which is accompanied by chronic inflammation and hepatocyte regeneration. Cells are at greater risk of genetic changes (mutations).
Which Hepatitis?
- member of Flaviviridae
- enveloped (E1 and E2 glycoproteins)
+SS Non-segmented RNA
(can serve as mRNA and translated in to a RNA polymerase)
Hep C
What are the functions of the Structural Proteins of Hep C Virus?
E1: _________
E2: _________
C: _________
E1: Fusion Protein
E2: Receptor Binding
C: Core Protein
Fact: Hepatitis C virus has taken over Chronic Active Hepatitis***
For Hep C, what is the primary mode of transmission in developed countries?
IV drug use
Fact - People at risk of acquiring HCV:
1) parenteral drug users
2) health care workers
3) hemodialysis patients
4) recipients of whole blood, blood cellular components or plasma- factor VIII now is treated to inactivate HIV, HBV and most likely HCV
5) sexual activity
6) Perinatal transmission also minor route
7) serum from donors of organs, tissue or semen intended for human use should be tested for anti- HCV by EIA
What are 3 classes of antiviral drugs for Hep C?
What vitamin may reduce viral replication?
*Most drugs treatment require co-admin with Peglyated Alpha Interferon is also beneficial.
- Protease inhibitor
- NS5A Inhibitor
- NS5B (RNA Polymerase) Inhibitor
Vitamin D
Which Hepatitis?
- requires HBV as a helper virus (contributes HBsAg which surrounds the RNA-HDAg complex)
- circular negative SS RNA
-HD Ag (delta antigen) binds to genomic RNA to yield virus core (only thing it can do!)
**ENHANCES THE SEVERITY OF HBV INFECTION**
Hepatitis D Virus
Which Hepatitis?
+ SS RNA
-fecal-oral transmission in contaminated drinking water and food
**SERIOUS FOR PREGNANT WOMEN (20-30% fatality rate)
- Acute infection yields lifetime immunity
- some evidence of animal reservoirs**
- Supportive treatment - rest, fluids, nutrition
-NO VACCINE
Hepatitis E Virus
