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91 Cards in this Set
- Front
- Back
What are some signs of hepatitis?
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Inc bilirubin
Inc AST Inc alkaline phosphatase |
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What is the job of the liver?
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Filter and metabolize toxins from the blood
Filter bilirubin (product of Hb) through the hepatic bile ducts by the gall bladder To the pancreatic duct, to the intestine |
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What happens at the Ampulla of Vafer?
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Common bile duct and pancreatic duct combine
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What are the 2 alternate causes of jaundice?
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Hepatocellular injury
Cholestasis |
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What happens if there is an injury to the hepatic cells?
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Damaged li er cells develop leaky mbs and don't keep their contents intracellular
Intracellular enz like AST escape into circulation |
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What happens in cholestasis?
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Liver cells are normal
->Have bililary obstruction or hepatic infiltration -Obsturcted/ damaged bile ducts induce Elevated Synthesis of alkaline phosphatase (AP) |
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Is bilirubin useful in distinguishing between cholestasis and hepatocellular injury?
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No, because it can be elevated in both
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What are the symptoms of someone who has any chronic liver disease?
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ilirubin almost normal
AST very elevated Alkaline phosphatase a little elevated |
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Which Ab is the first to rise in hepatitis infection?
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Anti-HAV IgM Ab
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What happens if you have Anti-HAV IgG Ab?
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Chronically infected with Hep A
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What is a marker for circulating HepB?
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Hep B surface Ag
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When does someone have anti HB Abs?
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After natural infection or the vaccine
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What is a marker of recovery and immunity vs Hep B?
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anti-HBs(surface) Ag
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Why should contraceptive pills not be taken if you have hepatitis?
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Toxic to the liver
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What kind of procedure is done to look at someone's liver?
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Percutaneous needly biopsy
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What is the only treatment for someone who has hepatocellular carcinoma?
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Liver transplant
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What happens during hepatic carcinoma?
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Get necrotic areas in the liver
Get calcified in the liver |
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When can hepatocellular carcinoma occur?
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Onnly in ppl who have liver damaeg |(cirrhosis due to alcohol) or who are chronically infected with HepB/C
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What is the progression of disease following acute hep infection?
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Acute infection --> Resolution of infection or chronic hepatitis
Chronic hep --> Mild- moderate disease or cirrhosis Cirrhosis --> Complications of portal hypertension or hepatocellular carcinoma Both of these can only be treated with a liver transplant Failure to get a transplant leads to death |
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What happens when there is fibrotic scar tissue on the liver?
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This tissue is very rigid and holds the normal tissue tightly
Doesn't let is regenerate and expand |
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HAV
Virus gp Transmission Carrier/chronic state |
Virus gp: Picornavirus (RNA)
Transmission: Fecal/oral (starts in GIT) Carrier/chronic state: No |
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HBV
Virus gp Transmission Carrier/chronic state |
Virus gp: Hepdnavirus (DNA)
Transmission: Blood/sex Carrier/chronic state: Yes |
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HCV
Virus gp Transmission Carrier/chronic state |
Virus gp: Flavivirus (RNA)
Transmission: Blood Carrier/chronic state: Yes |
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HDV
Virus gp Transmission Carrier/chronic state |
Virus gp: Viroid like
Transmission: Blood Carrier/chronic state: Yes |
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HEV
Virus gp Transmission Carrier/chronic state |
Virus gp: Calicyvirus
Transmission: Fecal/Oral Carrier/chronic state: No |
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HFV
Virus gp Transmission Carrier/chronic state |
Virus gp:Unknown
Transmission: Fecal/oral Carrier/chronic state: ? |
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What kind of viruses are HepE/F?
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Pnly acute
Very similar to Hep A Dif Epi (mostly South Asia) |
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W/hat is the only DNA hep virus?
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Hep B
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What is the size of hepA?
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27-29 nm
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What is the size of hep B?
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Small pleomorphic spherical particles: 22nm
Tubular forms double-shelled virus: 42 nm |
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How many forms does Hep b have?
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3
Has filamentous particles Have cores |
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Describe the acute infection pattern of Hep a/E/F
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Have viraemia and virus in the feces from week 2, before Ab begin to develop
Takess ~ 1 month to develop symptoms IgM peaks at about 6 weeks IgG peaks ~10 weeks |
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What is the geographical distribution of hep A?
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Where there isn't clean drinking water
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What is the Epi of Hep A?
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Young children
Promiscuous population |
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How many cases of Hep A are there per year in the States?
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20,000
Incidence has been decreasing since 1990s |
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What are th risk factors for HepA?
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Unknown > Personal contact > daycare > travel> outbreak=IDU
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Is hep A a severe problem?
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No, no death or chronic infection
There is a vaccine for it |
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Describe hep B
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Has a core with icosahedral symmetry
Covered with surface Ag Over produces surface Ag so that sometimes it aggregates by itseld, forms small sphere of filamentous particles without a core |
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What forms does Hep B come in?
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Full virus w/ core, has HBsAg
If disrupt with detergent --> Virus core with HBcAg Strong detergent again -->Soluble HBeAg released from the core + DNA thats circular but only partially ds |
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What kind of activity does HepB have?
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RT activity
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Describe how HepB is made
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Genomic circular DNA --> (acted on by virion enz and repair mech) ---> Closed circular DNA --> (+) strand mRNA --> ptns
Closed circular DNA can also become ---> geno,mic RNA -->Genomic DNA --> Progeny virus |
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What happens to the genomic DNA?
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Made into full length genomic RNA that is RT'd into genomic DNA that goes into the virus particle
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What are drugs vs Hep B against?
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Anti-RT/Anti-HIV modified drugs
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How many nucleotides are in HepB?
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32 nucleotides
(dsDNA) Very economical, doesn't habe any non-coding nuc in the genome |
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Where is the E Ag (HBe)?
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In the core (C) Ag
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How many cases of Hep B are there in the US/year?
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20,000
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What are the risk factors for HepB transmission?
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Heterosexual > Unknown> Drug abuse> Homosexual > household> healthcare
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In which body fluids is HepB in high concentration?
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Blood
Serum Wound exudates |
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In which body fluids is HepB in medium concentration?
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Semen
Vaginal fluid |
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In which body fluids is HepB in low concentration?
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Urine
Feces Sweat Tears Breatmilk Saliva |
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What are HepB's main modes of transmission?
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Sexual
Parenteral Perinatal |
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Who is at risk for sexual transmission?
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Sex workers and homosexuals
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Who is at risk for parenteral transmission?
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IVDA
Health workers |
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Who are at risk for perinatal transmission?
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Mothers who are HBeAg positive are much more likely to transmit to their offspring than those who are not
Perinatal transmission is the main means of transmission in high prevalence populations |
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What is the geographic distribution of HBV?
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In a lot of places, especially SE China
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How is chronic HBV infection mainly transmitted?
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Mother-child vertical tranmission
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Describe acute HepB virus infection
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Start with HBsAg. Disappears after 6-8 months
IgM anti-HBc appears after 1-2 months Anti-HBs Ab appear after ~ disappearance of HBs Ag -->Total anti-HBc plateaus and remains lifelong IgM eventually disappears |
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Describe CHRONIC hep B infection
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Never see anti HBs Ab
Anti-HBc never disappears HBsAg stays for life Eventually get anti-HBe Ab |
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What is the outcome of hep B infection?
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Of the infections that take place at birth 90% become chronic
In adults, only 10% of infections become chronic |
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What are the approved therapies for chronic hep B?
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IFN or pegIFN
Lamivudine Adefovir Entecavir Telbivudine |
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What's the problem with hepB?
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Can't eradicate it
But can keep the viral load low, suppress it -->Stop cirrhosis and liver cancer |
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How is hepC transmitted?
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By blood
-->Tranfusion or sharing needles |
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Describe hepC
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Icosahedral core
Surrounded by envelope +ssRNA 5'-3' end like Picornaviridaem but it's a flavivirus Has a single long open ptn coding reading frame Cleaved mainly by cellular proteases and virus into core ptns and internal cell ptns |
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How many cases of HepC are there in the US?
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40,000/yr (2x as much as hepA or B)
Has decreased a lot after increased screening for it in the blood |
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What are teh risk factors for acute HCV infection?
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Drug abuse > Low SES > Sexual/household > None > Transfusion > Healthcare > Dialysis
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Is this virus sexually transmitted?
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Probably not (unless bleeding)
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Where is HCV more prevalent?
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In poorer areas
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Describe the history of acute HCV infection
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Most ppl don't know they're acutely infected
HepC RNA initially strongly prevalent bu then goes to almost nothing -->Disappears and recurs (sometimes completely disappears) -In the ppl in which it periodically reappears, it leads to chronic hep cirrhosis and liver cancer (~20 years after infection) -80-90% of ppl go through this periodic infection recurrence |
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When was HCV discorvered?
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1989
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How were portions of the HCV genome isolated?
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By screening cDNA expression libraries made from RNA and DNA from chi,ps infected with seru, from a patient with post-transfusion non-A/B hep
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Describe Hep C genome
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Flavivirus
+ ssRNA ~10,000 nuc Encodes a single polyptb of ~3000 aa |
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Is there a cell culture system yet for HCV?
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No, also no non-primate model yet
--> .: difficult to make drugs |
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Is perinatal transmission important for this virus?
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Not really
Also, many ppl infected with HCV don;t have any specific risk factors |
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What are the consequences of HCV infection?
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85% of ppl acutely infected with HCV become chronically infected
HCV is a major cause of chronic hep Once chronically infected, the virus is almost never cleared without treatment In rare cases, HCV infection causes clinically acute disease and even liver failure |
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What are teh current treatment for hep C based on?
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IFN-a administered by injection
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What are the side effects of this treatment?
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Flu-like symptoms
Depression Rashes Abnormal blood counts |
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What else can be used in addition to IFN-a?
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Ribavirin
-->Together, htey are superior for treatment |
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How is the polyptn of HCV processed?
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By host and viral proteases into 3 major structural ptns and several non-structural ptns required for viral replication
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What were the new NS3 protease inhibitors marketed in 2011?
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Telaprivir
Boceprivir ->Dec proportion of non-responders to current therapy by 70-80% |
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What are the future treatments for chronic HepC?
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Specific Agents vs hep C virus ptns
a) Targeting the HCV RNA genome b) Cmpds directed vs HCV |
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What are the agents used to target the HCV RNA genome?
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1) Ribozymes cleaving the hepatitis C virus RNA
2) Antisense inhibitors complementary to HCV RNA 3) Inhibitors binding at the internal ribosome entry site (IRES) |
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What are the cmpds directed vs HCV?
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NS3 RNA pol
NS3 RNA helicase/protease NS5B RNA pol |
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What are the challenges to dev'p of a vaccine?
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HCV only elicits a weak immune response (even in actual infection)
Characteristics of a protective IR have been difficult to determine Considerable variability exist btw isolates at both the nucleotide and ptn lvl HCV mutates very easily in its Ag domains No effective small animal model or cell culture system |
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Describe HepD
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Defective virus
Needs a helper virus to infect humans (needs HepB) HepD makes its viral particles by encapsidation of its viral genome in a HBs Ag |
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What does the HepD virus have?
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delta Ag
HBs Ag RNA |
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What is the genomic distribution of HDV?
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Present everywhere that has high HepB .: maminly SE Asia
->Can't exist anywhere that doesn't have hepB |
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How does HepD use HepB?
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HepD sits in the HBsAg env
Its genome is also circular RNA |
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What does the RNA od HDV look like?
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Plant virions
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What kind of RNA does it encode?
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Long and short forms of delta Ag
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How does HDV cleave itself?
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Ribozyme activity in RNA to self cleave and ligate itself
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How is Hep E transmitted?
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Oral-fecal
No drug treatment/vaccine Causes diarrhea |