Hepatitis C

True

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

flavivirus

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

has almost nothing clinically in common with other arboviruses

method of transfer: the others are transferred by mosquitos, but Hep C is blood borne

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

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

• low number of circulating virions
• integrate into host genome

• acute hepatitis C:
• - generally benign with 80% getting no jaundice and it being a generally asymptomatic primary infection

70% of people with Hep C don't clear it initially; it goes chronic, resulting in cirrhosis, end-stage liver disease, hepatocellular carcinoma

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

• Snorting cocaine or other drugs
• occupational exposure
• body piercing and acupuncture with unsterilized needle
• tattooing
• mother to child
• non-sexual household contacts, such as sharing razors or toothbrushes
• sexual transmision: low risk in monogamous relationship
• unknown

• 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

ribavirin

• 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

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

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

flu like symptoms: headache, fatigue, muscle and joint aches, fever, chills

Psychiatric symptoms: depression, difficulty sleeping, difficulty concentrating, irritability

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