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True or False: It is the most common blood-borne infection in the USA.
incidence ins going down but we are still dealing with the after effects
Chronic is still on the rise from the previous boom of infection; can go on for decades; stays in our bodies even more
- Africa is hit hard
- Russia is as well
- Globally distributed disease
What kind of virus is Hep C
What is evasion of the immune response?
It is an RNA virus that mutates quickly.
Envelope proteins--E1 and E2--have a hypervariable region; the antigens that our body recognizes changes quickly
It can downregulate our innate immunity
PKR is an effector of host antiviral defense pathway; represses translation by phosphorylating eIF2
NS5A has other activities as well; less understood
What makes HCV different from other flaviviruses?
has almost nothing clinically in common with other arboviruses
method of transfer: the others are transferred by mosquitos, but Hep C is blood borne
How HCV functions is also different from other flaviviruses. How?
Flaviviruses don't acquire mutations often because they have to be able to infect our own cells and infect cells at the same time; so, there is a lot of selective pressure to maintain the same epitopes and the same general structure of the proteins
Hep C has none of this pressure; they mutate very quickly; it has also hampered our ability to study the virus
Why is HCV hard to study?
it does not grow in any conditions in the lab. You need samples from people with it.
there have been attempts to adapt the virus to the culture. When scientists try to do this with Hep C, by the time they it into the lab, it has acquired so many mutations that its barely worth studying
HCV also has a __. And, it does not __.
- low number of circulating virions
- integrate into host genome
Pathology of the HCV?
- acute hepatitis C:
- - generally benign with 80% getting no jaundice and it being a generally asymptomatic primary infection
When you get it, you don't realize you have it. Explain.
70% of people with Hep C don't clear it initially; it goes chronic, resulting in cirrhosis, end-stage liver disease, hepatocellular carcinoma
What are the high risk methods of infection?
Mostly serum related--> blood products, which is still a little mysterious
blood products and transfusions in the '80s
injection (IV) drug use--60% of all new infections
What are the low risk methods of infection?
- Snorting cocaine or other drugs
- occupational exposure
- body piercing and acupuncture with unsterilized needle
- mother to child
- non-sexual household contacts, such as sharing razors or toothbrushes
- sexual transmision: low risk in monogamous relationship
- We don't have a vaccine for it yet
- - Not a strong immune response against this virus, perhaps because of its mutation
Interferon: given by shot, usually 3x a week
Pegylated interferon: long-acting, taken once a week
Combination therapy-- interferon taken with ribavirin
We do have some decent drug treatments that are very similar to the Hep B drug
Drug of choice: __. What is it?
- Appears in multiple steps of the infection
- Another nucleoside analog
- Has some effects that you would expect an analog to have; but it also has some wonky effect
What are the wonky effects of this?
Can turn helper T cells from Th2 into Th1: That is important because Th1 tells the body you have a viral infection and they need to amp up the response. It helps hone the immune response
On the inside of your cells, it inhibits an enzyme involved in GTP synthesis: mess up cells that are trying to replicate; cause excess mutagenesis of HCV new particles
Ribavirin binds to numerous bases and does what?
gets incorporated and screws up the rest of the signals--mutagenesis
increases the rate of mismatches and end up overly mutagenizing the genes and proteins and subsequent rounds of infection
Side effects of interferon and ribavirin
flu like symptoms: headache, fatigue, muscle and joint aches, fever, chills
Psychiatric symptoms: depression, difficulty sleeping, difficulty concentrating, irritability
Does treatment work?
interferon alone: 10-15% chance of clearing the virus from the blood
interferon and ribavirin: up to 40% chance of clearing the virus
pegylated interferon alone: about the same as interferon and ribavirin--40%
pegylated interferon and ribavirin: up to 50% chance of clearing the virus