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What drug type is available for Hep C?
DAAs
What percent of people die from liver failure assoc. with Hep C?
1-5%
What percent of people clear Hep C in 3 months?
30%
What percent of Hep C is chronic?
70%
What percent of Hep C is acute?
30%
What percent of Hep C are unaware?
80%
How many new Hep C infections /year?
1.5 mil /yr
How many currently infected with Hep C?
70 mil/1% of world population
What is the risk of cirrhosis in 20 years with Hep C?
20-33%
What are the symptoms of Hep C?
Jaundice, nausea, fatigue
What are the assoc diseases of Hep C?
Liver cancer, cirrhosis, liver failure
What is the link between HCV and liver failure/transplant?
Most liver failures and transplants in US are as a result of Hep C infection
Why is there no Hep C vaccine?
Quasispecies
Mutates frequently
Latency
How does a DAA work?
Many drugs in one to target quasispecies of Hep C
How is Hep C diagnosed?
2 blood tests- antibodies then RNA
How is Hep C spread?
Blood contact (organ transplant, needle sharing, blood transfusions)
What are the associated cancers of EBV?
Mono (not cancer), epithelial carcinoma, B-cell lymphoma
What are the symptoms of EBV?
Liver cancer and disease
What is the drug for HSV1/2?
Ganciclovir
What are the symptoms of KSHV?
Spindle cell formation, lesions on internal organs, bleeding into lesions, RBC buildup/stuck in lesions
What are the causes of KSHV?
Organ transplant, body fluid contact, sex
What is the virus most responsible for liver cancer?
HBV
What is the chance to develop liver cancer with HBV?
15-40%
What are the transmission routes for HBV?
Vertical (endemic), blood contact, sex (US), organ transplants
How many liver cancer cases are there?
770k, mostly b/c of HBV
What are the types of HBV particle?
Small spheres (antigen)
Longer tubular (polypeptide)
Dane particle (infectious virion)
What percent of the world has had HBV?
25%
What are the chronicity rates of HBV?
90% if vertical
25-50% if 1-5 y/o
5% if adult
When is PeP given for HBV?
Newborn baby within 12 hours, 85-95% effective
What is PeP for HBV?
RBIG
Vaccine
What is the HBV vaccine?
Recombinant DNA, first licensed recombinant vaxx ever
How does the HBV vaxx work?
DNA grown in baker’s yeast → spheres purified → spheres purified to code for proteins → proteins picked up by immune system
What are the drugs available for HBV?
IFN- direct antiviral, fever effects
Nucleoside analogue- oral med, mild, targets replication
What is the Ebola drug?
Monoclonal antibody Remdisivir
What viruses use nucleoside analogues?
CMV, HSV1/2, Hep B
Which viruses have a vaccine?
COVID, Ebola, Rabies, Hep B, HPV
Which viruses use immunoglobulin passive transfer?
Rabies and Hep B
How does mRNA COVID-19 vaccine work once in the body?
mRNA for spike protein is injected and endocytosed
mRNA enters cytosol, translated into a protein via ribosome
Protein stimulates immune system
How does rabies infection work?
Rabies infection → rabies into tissue → rabies into neurons → rabies climbs up spinal cord into brain → replicates in brain → encephalitis → into saliva for transmission
How does EVD work?
Infects macrophages and liver → liver doesn’t produce clotting → macrophages recruited to liver → cytokine storm → blood vessels leak → lack of O2
Which viruses target the liver?
Ebola, CMV, Hep C, Hep B
What is the Ebola immune response?
IgG antibodies
How does WNV work?
Infection → diffusion into visceral organs → into spleen → crosses blood brain barrier → CNS → neuroinvasive
Which viruses are congenital?
CMV, HBV, HCV
What viruses are associated with transplants?
CMV, HBV, HCV, KSHV
Which viruses have an envelope?
All BUT HPV
Which viruses are DNA?
HBV, HPV, and all herpesviruses
How many HPVs are there?
300+
What genetic material is HPV?
DNA
Is HPV enveloped?
No- just capsid
What is the protein associated with HPV?
L1
How big is an HPV?
50 nm, very small
What part of HPV is recognized by the immune system?
L1 Protein
Is HPV specialized or generalized?
Extremely specialized to the point of body localization
What percent of people have had HPV?
50-80%
What is the most common STD?
HPV
What percent of people clear HPV and in how long?
90% in 2 years
How many deaths from cervical cancer yearly?
300k
How many cervical cancers are caused by HPV?
Majority, ~70%
How does HPV enter host?
Microabrasions
What percent of people get cervical HPV cancer in 30 years?
0.8%
What are the cancerous HPVs?
HPV 16 and 18
What are the benign HPVs?
HPV 6 and 11
How can HPV be prevented?
Vaccines
Protection
How is HPV detected?
Pap smears
Which HPVs are targeted by each HPV vaxx?
1: Cervarix, 16, 18
Gardasil, 16, 18, 6, 11
How effective is Gardasil 9?
90% of cervical cancers
Downside to HPV vaccines?
May need adjuvant
How does cancer, in general, work?
During replication, a cell makes a mistake and mutates, then that mutated cell multiplies and its multiplications mutate, etc
Why do old people get more cancers?
Acquire more mutated cells over a lifetime
What are the genes targeted by cancer?
Proto-oncogenes
Tumor-suppressing genes
What does a proto-oncogene do?
Supports cell proliferation
What happens when a proto-oncogene mutates?
Becomes an oncogene, proliferates rapidly and constantly
What does a tumor suppressor gene do?
Prevent unwanted mutant cell proliferation via apoptosis
What happens when a tumor suppressor cell mutates?
Loses ability to differentiate b etween mutating and non-mutating cells
How does HPV infect?
Basal cells in cervix → microabrasion allows HPV into cervix → HPV attaches to basal cells → HPV circularizes then linearizes its DNA → HPV DNA integrated into basal genome → new basal cells are made with HPV genome → virally infected cells express E6 and E7 → new proteins force cell proliferation > dying → cells proliferate more and more → genome packaging and virion assembly → virion release
What are the proteins E6 and E7?
HPV viral oncogenes
What happens when E6 and E7 are expressed?
E7 → E6 → deregulates cell proliferation → apoptosis blocked → outgrowth of deregulated cells → cancer
How long does cancer take to develop in a normal immune system?
15-20 years
How long does cancer take to develop in an immunocompromised system?
5-10 years
When does rabies become deadly?
Encephalitis once it reaches the brain and cardio-respiratory arrest