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152 Cards in this Set
- Front
- Back
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Hepatitis =
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'inflammation of the liver'
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List non-infectious causes of hepatitis
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Immunologic Damage, Toxic Damage (such as alcohol, drugs, poisons)
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HAV was isolated in what year?
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1973
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HBV was isolated in what year?
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1960s
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5 Hep Viruses
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Picornaviridae,
Hepadnaviridae, Flaviviridae, Deltavirus (viroid-like), Hepeviridae |
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How are HAV and HEV transmitted?
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Fecal-orally
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How are H(B/C/D)V transmitted?
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Parenteral, perinatal, sexually
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Define Acute
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Short term and/or severe.
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Define Chronic
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Lingering or lasting - may or may not be severe.
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Define Fuliment
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Developing quickly and lasting a short time, high
mortality rate. |
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Define Cirrhosis
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Hardening: may be the result of infection or toxins (e.g.
alcohol) |
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Define Jaundice
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Yellowing of the skin, eyes, etc due to raised levels of
bilirubin in the blood due to liver damage. |
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nonAnonB hep = hep __
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C
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Hep __ has a more crystalline structure
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A
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Hep ___ has a more rod like structure
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B
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Hep ___ has enveloped particles
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C
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Hep ___ & ___ are considered heterogenous
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D and E
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True or False
Acute hep infections can develop into fuliment |
True
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Draw the Types of Hep virus infections
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Hint- 5 categories are
1. Acute hep 2. chronic carrier (risk) 3. chronic hep (risk) 4. cirrhosis 5. Hepatocellular carcinoma (15541) See Slide 8 if you need help |
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___ is the largest cause of chronic liver disease
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HCV
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Characteristics of liver damage caused by hepatitis
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councilman-like bodies, bridging necrosis, cirrhosis, ground glass bodies
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For which types of Hep are there vaccinations for?
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Hep A and Hep B
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What hep vaccine is currently in developement?
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HEV
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What are some challenges to hep vaccines?
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_large amount of genetic variability
_in general, HCV elicits a weak immune response _characteristics of protective immunity are difficult to determine |
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____ and ____ analyses can determine the type and severity of Hepatitis virus infections
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Antibody and antigen
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Basic characteristics of Hep A virus
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Family: Picornaviridae
Genus Hepatavirus Non-enveloped, small icosahedral virus. Acute, self-limiting liver infection. ≤ Enterically transmitted |
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Draw the genome of HAV
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(+) ssRNA genome 7.5 KB
5’ terminal VPg, polyprotein - functions as a primer for RdRp to use in replication |
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HAV genome uses a polyprotein strategy- draw it out
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Here it is.
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True or False
HAV replication is poorly understood |
True
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Signs and symptoms of Hep A
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jaundice, nausea, fatigue, abdominal pain, diarrhea, loss of appetite
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True or False
You can have recurrent bouts of hepA |
False - it is an accute infection, you can get it only once
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Why do kids have a tendency to get hep A?
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Cause they poop and they dont wash their hands. Then they eat oreos.
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True or False
Hep A is sometimes asymptomatic in kids |
True- this is why its spread among kids faster as well- THEY DONT KNOW they have it
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Hep ____ always needs a helper virus
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D
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Besides food and water- what else is a high risk factor for hep A?
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International travel
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What does ALT indicate?
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it is an indication of liver damage
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When does viremia and fecal shedding generally occur in HepA?
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3-7 DAYS
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Draw the HAV events during the infection cycle
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*note IGM antibodes eventually are replaced by IgG antibodies
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What bodies fluids can you find HAV in?
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Feces, serum, and saliva (highest to lowest)
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Approximately what percent of people have been infected with HAV?
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33%
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How can you prevent HAV?
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Hygiene
Sanitation Vaccination Immune globin |
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True or False
In countries where children are the main reason high endemics of Hep A, vaccination is a MUST |
False - it's not recommended because kids can pass through the disease asymptomatically and not suffer like adults
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Quick details on HBV
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Family: Hepadnaviridae
Circular dsDNA with RT 42 nm enveloped icosahedral capsid. ≤ Four serotypes: o S Polymorphism o No pathological differences |
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What are the two hepanavirus generas?
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orthohepadnavirus and avihepadnavirus
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•Orthohepadnavirus
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Hepatitis B virus,
Ground Squirrel Hepatitis B Woodchuck Hepatitis B |
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Avihepadnavirus
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•Duck Hepatitis B
•Heron Hepatitis B Viruses. |
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Characteristics of viruses found in blood of hepB infected individuals?
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Blood from infected hosts contains large amounts
of small spherical and long filamentous particles with surface antigens. |
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Besides liver cells, what other cells do hep B viruses attack?
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Blood, spleen, pancreas
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HBV causes:
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chronic liver damage, hepatic carcinoma, and hepatitis
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Whats a Dane particle?
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The complete hepatitis B virion is called the Dane particle. It is a DNA virus of the Hepadna family and consists of an outer envelope and core.
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The envelopes of hepB have what surface antigen?
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HbsAG
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Core particles in hep B viruses are covered in what?
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HbcAG and viral DNA
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In Hep B which are more infectious - dane particles, or coreless particles.
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Dane- the empty spherical
envelopes & long filamentous envelopes consisting of cellular lipids and HBsAg are non infectious |
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HAV is inactivated by what?
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Formulin treatment
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How many doses total do you need for HAV immunity?
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3
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How many inactivated hepA vaccinations are there?
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About 4
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Whats the point of Hep B's empty shell?
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It can still attach and neutralize the host cell because the surface proteins can still be infectious
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Review Dane particle assembly
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See slide 34 and 35
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Give the characteristics of Hep B Genome
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ss and dsDNA genome
≤ Long Strand (-) DNA -5’ covalently linked RT with 3’ & 5’ ends overlapping. ≤ Short Strand (+) DNA Variable length - 5’ end covalently attached to capped RNA oligomer ≤ Overlapping genes! |
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Where does hep B transcription occur?
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In nucleus!
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True or False
Hep B uses its own RNA polymerase |
False - it uses host polymerase
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List the products of hep B transcription
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5 different promoters
5 transcripts (mRNAs) all capped and polyadenylated all share the same 3’ end 2 enhancer elements- EN1 and EN2 |
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List the proteins of Hep B and their functions
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E protein: made early, may suppress host immune system
C protein: major component of nucleocapsid P protein - reverse transcriptase LS, MS, SS - surface proteins have common C-termini involved in envelope formation X protein - ? implicated in development of hepatocellular carcinoma |
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HBV Entry into Hepatacytes
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Little is known!
≤ PreS1 proteins bind cellular receptors ≤ Entry is pH independent plasma membrane fusion (probably!). ≤ Viral cores transported to nucleus where DNA is released. |
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True or False
Almost all HBV DNA is produced by RT |
True
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Review Slide 40 & 41
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Use other book if you dont get it still
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True or False
Symptoms of HBV resemble those of HAV |
True
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Symptoms of HBV include
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Jaundice, fatigue, abdominal pain, loss of apetite, nausea, vomitting, joint pain
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Chronic infection in HBV occurs in...
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90% of children infected at birth, 30% of children infected at age 1-5, 6% infected after age 5,
and! death occurs in 15-25% of chronically infected persons |
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HBV prevention?
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Get vaccinated!
Preggos with Hep B should get HBIG (hep b immune globin) to protect their babies |
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Acute infection Hep B characteristics?
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-Asymptomatic incubation period 1-6 months with hi viremia, infection (though not necessarily to toxic effect) of hepatocytes, clearance from serum (HBsAG neg), clearance from liver
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Chronic infection of Hep B characteristics?
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High expression of viral X genes and tumor supressor gene mutation (p53)
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Draw Acute HBV infection with
recovery. |
NOTICE HBsAG eventually goes to zero!
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Draw Progression to chronic
HBV infection. |
NOTICE- HBsAg NEVER goes to zero!
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Describe the Mechanism of HBV Liver Injury
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CTL affects against HBcAg + or HBeAg+
-Direct cytotoxic effects of HBcAg -High levels of large HBsAg - ineffecient secretion (ground glass) |
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90% of chronic Hep B carriers are ______
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infants
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Demographic of chronic hep B infections?
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More than 8% of
population in all of sub-Saharan Africa, South East Asia, China, India, Indonesia, North Korea, the Phillipines, Haiti and others. China: 500,000 - 1 million new cases of hepatocellular carcinoma per year. Taiwan: Relative risk of getting HCC is 217 x risk of non-carriers. Hainan Island: Has highest levels of HBV in China and the highest levels of liver cancer. |
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People with chronic
hepatitis are more than ____ times more likely to develop liver cancer than the general population. |
100
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When and who should you give passive immunisation with HB immuneglobin?
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Within 12 hours after birth (infants)
48 hours after Body splash/NSI |
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Recombinant HBsAG vaccine works against _____ and should be given at ___ intervals
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surface proteins
0,1,6 month (dose time intervals) |
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What reverse transcriptase inhibitors are used in antiviral drugs for HBV
whats the problem, yo? |
Lamivudine, Famciclovir, Adefovir,
They all have to be given for a long time, and some HBV have developed drug resistant mutants |
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What cytokines are used in antiviral drugs for HBV?
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Interferon, liver transplant
Note- interferone blocks cirrhosis and cancer - but has to be given for 6 months up to a year! |
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What is the plasma derived vaccine for Hep B and its characteristics?
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Heptavax-B
1,1,6 intramuscular injections with 96% of young adults seroconverting Both vaccines protect against active Hepatitis B, asymptomatic HBV, the Carrier State, & HDV. |
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What is the recombinant DNA vaccine for Hep B and its characteristics?
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Recombivax engerix-B
Uses recombinant DNA in yeast with a 99% seroconversion rate in ages 20-29 Both vaccines protect against active Hepatitis B, asymptomatic HBV, the Carrier State, & HDV. |
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How long you should you wait after you get hep B vaccine to see if it is effective?
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6 months
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What should you treat chronic hep B with?
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Interferon alfa-2b, pegylated interferon alfa-2a, adefovir, lamivudine, entecavir, telebivudine
(there are 6) |
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What is GAVI?
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Global alliance for vaccine for vaccines and immunization distributes funds for 3 year supply of autosyringes
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Pregnant women who have hep B are ____ positibe
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HBeAg
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___ % of chronic hep B infections are aquirred perinatally.
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30
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Hep B vaccination in SEAR (what does SEAR stand for?)
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Southeast asia region
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GAVI provides for ____ newborns in china to get hep B vaccine.
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50 -But chinese govt kicks in the other 50 so ALL newborns get vaccinated
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India: ___ hepatitis B vaccine and safe injection projects.
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45
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Single use disposable syringe used in indonesia (provided by GAVI - who provides other treatments?)
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Uniject
Indonesia provides doses 2 & 3 |
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Quick details on HDV
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Viroid (ribozyme) & mRNA
(protein coding) ≤ Relies on HBV for packaging. |
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Outer proteins on HDV envelope are what?
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HBV, L, M, and S
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Inner nucleocapsid of HDV consists of what?
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HDV genomic RNA with HDAg-D, and HDAg-S
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define satellite virus and give an example.
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term used in plant virology for a virus associated functionally, at least for the purpose of its own replication, with another virus.
dependoviruses are DNA satellites of Adenoviruses. |
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True or False
Satellite Viruses are often parasitic on the helper virus by reducing symptoms and interfering with the replication of the helper virus. |
True
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The smallest pathogens are ____.
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viroids
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True or False
Viroids do not have enough DNA to self replicate |
False- they do self replicate
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VIroids are known to induce disease in ____.
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plants
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Whats weird about viroids?
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They don't have any mRNA or encoded proteins!
They replicate using a rolling circle mechanism! |
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Draw a viroid and list its characteristics
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Very small, covalently closed, circular RNA molecules capable of
autonomous replication and induction of disease. • Sizes range from 246-401 nucleotides. • Ten Times smaller than the smallest RNA viruses. • No coding capacity - do not encode their own polymerase. • Use host-encoded polymerases for replication. • “Classical” viroids have been found only in plants. |
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True or False
Viroids can induce severe symptoms |
TRUE
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HDV needs ___.
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HBV
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Viroids replicate using _____ enzymes
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host
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Whats beneficial about satellites
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They can encode a protein not found in a virus
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In HDV the genomic RNA is the ____ strand
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+
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Draw the rolling circle mechanism
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Explain
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Define ribozymes
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RNA molecules with enzymatic activity. They
are able to cut themselves and other RNAs into smaller pieces. |
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Which hep virus utilizes ribozyme activities?
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HDV- in both positive and negative rolling strands
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______ and ______ ribozymes are used in processing of
viroids and some satellite RNAs. |
hammerhead and hairpin
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Hepatitis Delta is a chimeric molecule- what does that mean?
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half viroid/half satellite RNA
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What are the viroid like properties of the HDV virus?
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Rod-like circular RNA.
- Central conserved region similar to plant viroids. - Rolling circle replication - Ribozyme Self-cleaving activty. |
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What are the satellite like properties of HDV?
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encodes a protein
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Why does HDV need HBV?
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For surface membrane proteins used in encapsidation- can replicate okay by itself however
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HDV is ___ sense ____
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- sense
SSRNA |
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Nuclear RNA synthesis of HDV
via ____ |
DdRp !!!
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How does HDV switch to strand replication from
mRNA transcription? |
Switch to full length (+)
via suppression of poly (A) tail. |
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What is the most highly active ribozyme known?
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HDV
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simultaneous HBV & HDV infections = ___
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coninfection
(high initial IgM (anti HDV) |
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infection by HBV followed by infection with HDV =
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superinfection
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Coninfection
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Coinfection or superinfection of HDV?
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Superinfection
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Coinfection or Superinfection of HDV
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Envelop glycoproteins of hep C?
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E1 and E2
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Basics of Hep C
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Enveloped capsid with
icosahedral symmetry. Family: Flaviviridae +SS RNA |
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Flaviviridae causes what diseases?
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Yellow fever virus, dengue, west nile
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Three Flaviviridae Genera?
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Flavivirus
Pestavirus Hepacivirus |
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Flavivirus genera causes -
(flaviviridae) |
Central European encephalitis (TBE-W), Japanese encephalitis (JE), St. Louis
encephalitis (SLE), West Nile virus (WN), Dengue (DEN), Yellow fever (YF) |
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Pestivirus Genus causes
(Flaviviridae) |
Bovine viral diarrhea (BVDV), hog cholera or classical swine fever (CSFV)
Very important Animal Diseases |
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Genus Hepacivirus causes
(flaviviridae) |
Hep C
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HCV genome describe it
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5’ non-translated region (IRES)
≤ Single ORF of ~9,000 nts. o Translated into polyprotein and processed by viral & cell proteases ≤ Short 3’ non-translated region |
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Symptoms of Hep C
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jaundice, nausea, vomitting, abdominal pain, dark urine, fatigue, loss of appetite
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Chronic infection of hep c occurs in ___% of individuals and of these chronic liver disease occurs in ___% of the individuals
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55-85%
70% |
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Ways to get hep C
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Yo Mama and sharing drug needles
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Incubation period for hep C?
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6-8 weeks
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Damage from hep c due to?
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damage due to cell mediated immune response
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Extrahepatic manifestatiosn of HCV?
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EW
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Highest cause of hep C (in order?
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Drug use - 60%
Sexual - 18% Unknown - 9% Perinatal (occupational) - 5% |
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True or False
Blood transfusions are a high source of hep C |
False - diagnostic tests have virtually eliminated this pathway
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Why isn't there a hep c vaccine yet?
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Vaccines have not been developed because:
-virus is poorly immunogenic -immune responses are thought to cause more serious disease. -variation in DNA protein sequences between isolates |
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True or False
Several HCV Subtypes Exist |
True
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Two drugs for chronic hep C?
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Interferon and ribavirin
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Read the medical treatment part for Hep C
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This is weird because I thought there wasnt any cure for hep C!
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True or False
Over the next decade liver cancer deaths caused by HCV may exceed Those caused by HIV/AIDS. |
True
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Course of disease in Hep C please
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Accute hep C --> chronic infectioin --> chronic liver disease -->cirrhosis --> HCC and decomposition
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Hepatitis E virus (HEV)QUICKIE
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Hepeviridae
≤ Wide genetic variation. ≤ Icosahedral nonenveloped capsid. ≤ Difficult to isolate authentic viral particles. |
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HEP E is usually caused by
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drinking poopy water in weird foreign countries
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Clinical features of Hep E?
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Fatality rate is higher than HIV!
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How do avoid hep E
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Dont drink funny water with funny ice
Dont eat funny shellfish dont eat uncooked fruits or veggies unless you peeled or made it yourself |
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True or False
IG from western donors was helpful in the production of a vaccine |
FALSE
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Is there a hep E vaccine?
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Sort of- only a 6 month trial so far, glaxosmithkline makes it.
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