Micro 2 Ex 2

Front 1

Hepatitis A Virus Transmission

Back 1

Fecal-oral
Close personal contact(e.g., household contact, sex contact, child day care centers)
Contaminated food, water(e.g., infected food handlers)
Blood exposure (rare)(e.g., injecting drug use, transfusion)

Front 2

Whats special about HAV capsid?

Back 2

Capsid is more stable than other picornaviruses

Stable to:
Acid at pH 1
Detergents
Saltwater & groundwater (months)
Drying
High & low temperatures

Front 3

HAV capsid is inactivated by

Back 3

chlorine treatment of drinking water
formalin/formaldehyde
UV radiation

Front 4

HAV is mostly concentrated in

Back 4

Feces>serum>saliva

Front 5

Hepatitis A –Incubation period is notable because

Back 5

It is longer than other piconaviruses. It replicated slower. INFECTIOUS SPREAD because you are asymptomatic during this period yet the virus is still replicating.

Front 6

What age group is more prone to jaundice by HAV?

Back 6

older than 14, the younger the less chance of getting it

Front 7

What are the chronic manifestations of HAV?

Back 7

None everyone clears the infection up.

Front 8

Hepatitis A infection

Back 8

1. Viremia
2. ALT and IGM rise
3. IgG antibodies rise and protect you in the future

Front 9

HAV Acute illness lab results

Back 9

the detection of HAV-IgM in serum by EIA.

Direct Detection – RT-PCR of feces. Can detect illness earlier than serology

Front 10

Past HAV infections can be detected by

Back 10

the detection of HAV-IgG by EIA.

Front 11

fatigue, abdominal pain, loss of appetite, intermittent nausea, vomiting)
jaundice or elevated serum aminotransferase levels

Back 11

Acute HAV

Front 12

Prevention of Hepatitis A

Back 12

Vaccination (pre-exposure)
Immune globulin (pre- & post-exposure)

Good hygiene
Clean water systems; avoidance of food contamination

Front 13

Two HAV vaccines are currently licensed in the United States

Back 13

HAVRIX® (manufactured by GlaxoSmithKline)
VAQTA® (manufactured by Merck & Co., Inc)
Made of inactivated virus adsorbed to an adjuvant
administered by intramuscular injection in the deltoid

Front 14

Who should you vaccinate against HAV?

Back 14

-Routine Childhood Vaccination is recommended
-Persons at increased risk for infection
travelers to intermediate and high HAV-endemic countries
MSM (Men who have sex with men)
injection drug users
-Persons at increased risk of complications
Persons who have clotting factor disorders
Persons with chronic liver disease

Front 15

Vaccination characteristics

Back 15

No cases in vaccinated children at follow-up

Persistence of antibody
At least 5-8 years and up to 20 yrs

Front 16

Post exposure vaccinations to HAV should be adminestered

Back 16

within 14 days) and it occurs usually in
household and other intimate contacts
institutions (e.g., day care centers)
common source exposure

Front 17

Hepatitis A Virus
Picornaviridae biology

Back 17

nonenveloped virus
Positive-strand RNA genome

Front 18

HAV Genome Internal Ribosome Entry Site in 5’ UTR

Back 18

5’ UTR

(common characteristic of picornaviruses)
(where cell ribosomes bind to initiate viral proteins synthesis)
Encodes a single Open Reading Frame (ORF)
Translates one long viral Polyprotein

Front 19

HAV Life Cycle

Back 19

Entry:
-Virus Binds to Receptor
-Endocytosed
2. Genome is released
3. VPg Removed
RNA translated
4. Polyprotein Cleavage
(assemble on membranes)
5. Replication:
(minus-strand synthesis)
6. Replication:
(positive-strand synthesis)

Translation
Template for (-)
Packaged
8. Particle Assembly
9. NONCYTOLIC Particle Release by exocytosis

Front 20

HAV Summary Basic Virology

Back 20

Picornavirus
One serotype
Noncytolytic

Front 21

HCV Summary Epidemiology

Back 21

Blood
Incidence of clinical disease increasing

Front 22

HCV Summary Clinical Manifestations

Back 22

Usually Chronic
Progression dependent upon multiple host & viral factors

Front 23

HCV Basic Summary Virology

Back 23

Flavivirus
Six Genotypes, multiple subtypes, quasispecies

Front 24

Hepatitis C Virus Transmission Risk Factors

Back 24

Received blood products prior to 1992
Shared drug paraphernalia
Stuck by a used blood needle
Kidney dialysis
Tattoo or body piercing
Multiple sex partners or sexual activity involving contact with blood
Shared personal care items (razors, toothbrushes)
Incarceration
Combat veteran

Front 25

The number one cause of chronic hepatitis in the US is

Back 25

HCV

Front 26

The number one cause of chronic hepatitis in the world is

Back 26

HBV

Front 27

70% asymptomatic, sometimes mild jaundice and malaise, ab pain

Back 27

acute HCV

Front 28

persistent hepatitis
steatosis
insulin-resistance
liver cirrhosis
hepatocellular carcinoma

Back 28

Chronic HCV

Front 29

Does anti-HCV confer immunity?

Back 29

No

Front 30

Whats the difference between acute and chronic HCV infections?

Back 30

In acute infection, rise of antiHCV leads to decrease of ALT. In chronic, antiHCV remain high, but ALT fluctuates between high and low concentrations over the years.

Front 31

Clinical Symptoms of HCV

Back 31

impaired cognitive functions
digestive disturbances
low grade fevers
abdominal discomfort
appetite disturbances

fatigue
depression
anxiety
many others

Front 32

The first test to test for HCV is

Back 32

HCV antibody

Not useful in the acute phase
Can not distinguish current from past infection

Front 33

what test is used to determine acute or chronic HCV?

Back 33

HCV-RNA - RT-qPCR

Use widely for monitoring the response to antiviral therapy).

Front 34

What are ALT (Alanine Aminotransferase )
AST (Aspartate Aminotransferase)
good for?

Back 34

elevations indicate inflammation and hepatocyte damage
provide no information about the presence or absence of fibrosis, cirrhosis, or functional hepatic impairment

Front 35

Measure of liver function
via molecules like

Back 35

platelet count
Bilirubin
Albumin
Cholesterol

Front 36

Manifestations of Liver Disease

Back 36

Icteric Symptoms
Portal Hypertension
Palmar erythema
Increased estrogen
Gynecomastia, testicular shrinkage
Ascites (due to low albumin)
Visible veins
Spider angiomata, caput madusa, varices
Asterixis
Encephalopathy

Front 37

Helps objectively provide a specific diagnosis
Aids in determining the severity of inflammation
Aids in determining degree of fibrosis & cirrhosis
Evaluate for other causes of chronic liver disease
iron overload, fatty liver, and others
Aids in treatment recommendations

Back 37

Liver Biopsy in HCV

Front 38

HCV Genotype 3a associated with

Back 38

higher steatosis

Front 39

HCV Genotype 1a/1b less respond to

Back 39

interferon-based therapy:
45% sustained response to peg- IFN + ribavirin

Front 40

HCV genotype 2/3 more likely to respond to

Back 40

more likely to respond to interferon-based therapy
70-80% sustained response to peg- IFN + ribavirin

Front 41

Treatment of Hepatitis C

Back 41

No preventative vaccine

Treatment has limited efficacy
Interferon and Ribavirin
Only a fraction of patients respond
Toxic Side effects
Expensive
Protease Inhibitors FDA Approved
New Inhibitors on the horizon

Front 42

HCV response to IFN was highly increased after the addition of

Back 42

Ribavirin

Front 43

What are the problems of HCV tx?

Back 43

Long treatment duration with cause toxic side effects
IFN generally activates patient immune response (flu)
IFN must be injected (with PEG-IFN only 1/wk)
Host factors limit efficacy

Front 44

Which genotype is more resistant to HCV IFN tx?

Back 44

Genotype 1 and also The most prevalent HCV genotype in the US

Front 45

Whats the relation between weight and HCV response?

Back 45

Obesity decreases the efficacy of tx. Sustained Virologic Response (SVR) is decreased

Front 46

Who is more affected by HCV?

Back 46

African Americans

Front 47

Does health of the liver affect HCV tx?

Back 47

Yes, the healthier the liver the better the response

Front 48

HCV genome

Back 48

Family: Flaviviridae (enveloped, positive-strand RNA viruses)

contains a single ORF that encodes a polyprotein (~3011aa)
5’ => Structural proteins
3’ => Non-structural proteins
ORF is flanked by highly structured 5’ and 3’ non-translated regions
5’ NTR contains an internal ribosome entry site (IRES) for translation
Polyprotein processed by host & viral proteases

Front 49

Specific Targets for HCV Treatment

Back 49

Protease and Polymerase Inhibition

Front 50

Specific Targets for HCV Treatment:NON-enzymatic targets

Back 50

NS5A is a multifunctional proteins required for
Replication and capsid assembly

Front 51

Specific Targets for HCV Treatment:Cellular Factors

Back 51

Required for replication
Required for assembly & release
Required for particle entry into cells

Front 52

Whats the challenge in making a vaccine against HCV?

Back 52

NS5B is the viral RNA polymerase:
Has a very high error rate
Has no intrinsic repair mechanism

High degree of genetic variability resulting in global diversity:
Six major genotypes consisting of numerous subtypes
Within individual patients exists as a quasispecies

**Significant challenge for vaccine development**

Front 53

HCV life cycle

Back 53

1) receptor binds to the surface of liver cell
2) Viral lipid coat merges with plasma membrane and it is endocytosed
3) Genome is released into cytoplasm
4) IRES recognizes - strand and makes + Strand of RNA
5) Viral replication complex is formed (membranous web)
6) Virion is assembled and maturates
7)Viral release.
8) host cells die eventually of exhaustion from budding off visions