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Micro Exam 2 > Yoshimura: Hepatitis Viruses > Flashcards

Yoshimura: Hepatitis Viruses Flashcards

1
Q

Hepatitis

Definition:
Main clinical features (4)

A

Hepatitis: inflammation and damage of the liver

Main clinical features:
o	Liver enlargement
o	Jaundice
o	Abdominal pain
o	Fever
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2
Q

Hepatitis

Other symptoms:
Can be caused by:

A

Other symptoms: lassitude (diminished energy), anorexia, weakness, N/V, chills and dark urine

Can be caused by: bacteria, protozoa, drugs, toxins and viruses (most important cause)

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3
Q

Hepatitis can assume two different phases:

A

Hepatitis can assume two different phases: acute and chronic.

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4
Q

Acute hepatitis produces:

How long does chronic phase last? Can result in?

A

Acute hepatitis produces temporary symptoms but depending on the virus can lead to chronic hepatitis.

Chronic phase lasts over a long period of time and can result in liver tumors (hepatomas).

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5
Q

What is the only hepadnavirus to infect humans?

What does HDV require to replicate?

A

HBV: only hepadnavirus to infect humans

HDV: viroid or satellite virus that requires HBV to replicate

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6
Q

Hep A

Family
Genus
Virion
Envelope
Genome
Transmission
Prevalence
Fulminant Disease
Chronic Disease
Oncogenic
A

Hep A

Picornaviridae*
Heparnavirus
Icosahedral
No
ssRNA
Fecal-oral
High
Rare
Never
No
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7
Q

Hep B

Family
Genus
Virion
Envelope
Genome
Transmission
Prevalence
Fulminant Disease
Chronic Disease
Oncogenic
A

Hep B

Hepadnaviridae*
Orthohepadnavirus
Spherical
Yes
dsDNA
Parenteral
High
Rare
Often
Yes
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8
Q

Hep C

Family
Genus
Virion
Envelope
Genome
Transmission
Prevalence
Fulminant Disease
Chronic Disease
Oncogenic
A

Hep C

Flaviviridae* (Family include yellow fever virus)
Hep-c-virus
Spherical
Yes
ssRNA
Parenteral
Moderate
Rare
Often
Yes
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9
Q

Hep D

Family
Genus
Virion
Envelope
Genome
Transmission
Prevalence
Fulminant Disease
Chronic Disease
Oncogenic
A

Hep D

Unclassified
Deltavirus
Spherical
Yes
ssRNA
Parenteral
Low, regional
Frequent
Often
?
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10
Q

Hep E

Family
Genus
Virion
Envelope
Genome
Transmission
Prevalence
Fulminant Disease
Chronic Disease
Oncogenic
A

Hep E

Hepevirus
Hepevirus
Icosahedral
No
ssRNA
Fecal-oral
Regional
In pregnancy
Never
No
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11
Q

Hep F/G

Family
Genus
Virion
Envelope
Genome
Transmission
Prevalence
Fulminant Disease
Chronic Disease
Oncogenic
A

Hep F/G

Flaviviridae
?
?
?
?
?
?
?
?
?
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12
Q

Other Viruses Causing Sporadic Hepatitis (6):

A 
o	EBV
o	CMV
o	HSV
o	Yellow fever virus 
o	Rubella virus
o	Enteroviruses
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13
Q

Cell Tropism Accounts for Similar Symptoms

What is cell/tissue tropism dependent upon?

Many symptoms of acute hepatitis due to:

A

Cell/tissue tropism of a virus dependent on cellular receptors that can bind viral surface proteins

Many symptoms of acute hepatitis due to the damage/cytolysis of liver cells (hepatocytes)

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14
Q

Cell Tropism Accounts for Similar Symptoms

Damage to Hepatocytes Can Occur Two Ways:
Examples:

A

Damage to Hepatocytes Can Occur Two Ways:

Direct: cytolytic effect by virus (ie. HCV replication is cytopathic)

Indirect: immune response to infection (ie. chronic disease caused by HBV result of immune response of cytotoxic T cells)

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15
Q

Cell Tropism Accounts for Similar Symptoms

Other cell types can also be infected:

Where does HBV replicate? (5)
What can be lymphotrophic?

A

Other cell types can also be infected:

o HBV replicates in spleen, gonads, kidneys, LNs and blood mononuclear cells
o HCV may also be lymphotropic (infects lymphocytes)

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16
Q

Acute and Chronic Infections

Acute Infections:
What hepatitis viruses can cause acute hepatitis?
In what cases can primary infection may be asymptomatic? (2)

A

Acute and Chronic Infections:

Acute Infections: all hepatitis viruses can cause acute hepatitis to varying degrees

In some cases, primary infection may be asymptomatic: HBV and HAV

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17
Q

Acute and Chronic Infections

Chronic Infections:
For what viruses can primary infection cause chronic infection?

A

Chronic Infections: HBV, HCV and HDV primary infections can lead to a state of persistent/chronic infection.

18
Q

Hepatic Cellular Carcinoma (HCC)

Definition:
Common with which hepatitis viruses?
Progression:

A

Hepatic Cellular Carcinoma (HCC): a common sequelae of chronic infection with HBV, HCV and HDV

Basics: gradual progression to cirrhosis and then to HCC (takes 25-50 years after primary infection)

19
Q

Hepatic Cellular Carcinoma (HCC)

Prevalence:
Causes:

A

Prevalence: accounts for 90% of primary malignant tumors of the liver (but fairly uncommon in the US and other developed countries)

Causes: constant inflammation and stimulation of cellular replacement induces multiple mutations in hepatocytes, eventually leading to tumor formation.

20
Q

HEPATITIS B VIRUS (HBV)
Pathogenesis

Transmission:

A

Transmission: primary infection due to sexual contact with infected host or from parenteral exposure to virus-containing blood/blood products

21
Q

HEPATITIS B VIRUS (HBV)
Pathogenesis

Degrees of liver injury:

Incubation period:

What happens to the majority?

A

Primary Infection:

Asymptomatic, OR
Varying degrees of acute liver injury (acute hepatitis)

Incubation Period: 45-180 days

Vast majority resolve the primary infection: however, ~5% will go on to a persistent infection characterized by active viral replication in hepatocytes and varying degrees of viremia

22
Q

HEPATITIS B VIRUS (HBV)
Pathogenesis

Chronic/Persistent Infection

Degrees of chronic liver injury:
What can be fatal?
What are those who live with symptomatic HBV at risk for developing?

A

Many are asymptomatic carriers (major reservoirs for spread of infection)

Others have varying grades of chronic liver injury and inflammation

  • Severe chronic hepatitis can be fatal (5-year survival rates only ~50%)
  • Others who live longer with symptomatic HBV at risk for developing HCC.
23
Q

HEPATITIS B VIRUS (HBV)
Structure

HBV Particle Morphology: virions consist of multiple types of particles: (3)

A

Fully mature and infectious virions (Dane particle): only ones that contain genomic DNA

20nm spheres: usually the predominant form (up to 1 million times more than Dane particles); do not contain any nucleic acid, and are not infectious

Filamentous particles (20nm diameter): variable length, do not contain any nucleic acid, and are not infectious

24
Q

HEPATITIS B VIRUS (HBV)

What is the only form with genomic DNA?

What is the predominant form?

A

Dane particle

20nm spheres

25
Q

HEPATITIS B VIRUS (HBV)

HBV Surface Antigen (HBsAg): What form has this?

What is a sensitive diagnostic test for HBV infection?

A

HBV Surface Antigen (HBsAg): all 3 forms have this common Ag on their surface

Direct detection of this Ag is a sensitive diagnostic test for HBV infection

26
Q

HEPATITIS B VIRUS (HBV)

What is the major structural protein that makes up the inner layer of the virion?

Presence of what is indicative of a recent HBV infection?

A

Hepatitis B Core Antigen (HBcAg): major structural protein that makes up the inner layer of the virion

Presence of IgM Abs to this Ag is indicative of a recent infection by HBV

27
Q

HEPATITIS B VIRUS (HBV)
Viral Genome

Shape:
Type:
Unusual structure:

A

o Circular, dsDNA genome (partially duplex)

o Unusual Structure: minus strand is full length; plus strand is of variable length(20-80% of minus)

28
Q

HEPATITIS B VIRUS (HBV)
Replication Cycle

What happens after infection?
What does host cellular poly II do?
What is packaged into core proteins?
What happens here?

A

After infection, partially dsDNA converted to fully dsDNA in nucleus of infected cell

Minus-strand DNA transcribed to full-length +RNA intermediate by host cellular polymerase II
- Transcribes 2.1, 2.4 and 3.5kb mRNA (only 3.5kb is encapsulated)

Full-length +RNA template (3.5kb) packaged into newly synthesized core proteins, where it is copied into full-length minus-strand DNA, using virally encoded RNA/DNA-dependent DNA polymerase (P protein), which has reverse transcriptase activity (RNA–>DNA)

29
Q

HEPATITIS B VIRUS (HBV)
Replication Cycle

What is copied by the viral DNA polymerase to produce a partial plus-strand DNA?

What does the core acquire in the process of release?

A

Full-length minus strand DNA is copied by the viral DNA polymerase to produce a partial plus-strand DNA
- Not clear why the full strand isn’t synthesized

Core acquires the HBsAg-containing envelope in the process of release from an infected cell

30
Q

HEPATITIS B VIRUS (HBV)

Prevention and Treatment:

A

Prevention: recombinant vaccine (first successful one developed for human infectious disease)

Treatment:
o IFN-alpha
o Inhibitors of HBV polymerase

31
Q

HEPATITIS D VIRUS (HDV)

What is HDV?
What does HBV provide to HDV?

Genome Size:
Type:
Encodes:

A

• HDV is a Viroid (Not a True Virus):

  • Cannot independently replicate in a cell
  • Satellite virus that requires HBV, which provides the HBsAg for encapsulation of the HDV viral genome

• Genome: has the smallest genome of all the RNA viruses and is circular (unique)

  • Negative ssRNA
  • Encodes a single viral protein (delta Ag) that functions in RNA encapsulation
32
Q

HEPATITIS D VIRUS (HDV)

What is diagnostic of infection?
Superinfection can lead to:
What happens to those who survive?

A

Delta Antigen: presence of anti-delta IgM diagnostic of infection

Superinfection: coinfection with HBV or superinfection of individuals preinfected with HBV can occur

  • Superinfection can lead to fulminant hepatitis with a high mortality rate
  • Those that survive the acute infection are chronically infected
33
Q

HEPATITIS C VIRUS (HCV)

Leading cause of:
Leading reason for:

A

HEPATITIS C VIRUS (HCV):
• General:
- Leading cause of post-infusion hepatitis
- Leading reason for liver transplants

34
Q

HEPATITIS C VIRUS (HCV)

Genome type:
Transmission: (4)

A

Genome: linear, +ssRNA (flavivirus)

Transmission:

  • Blood transfusion
  • Injection drug use
  • Mother to child (not common)
  • Sexual contact
35
Q

HEPATITIS C VIRUS (HCV)

Incubation Period:
Chronic Infection occurs in what %? What % go on to HCC?
Treatment:

A

Incubation Period: 6-7 weeks

Chronic Infection: occurs in 60-85%of HCV infections; 2-7% go on to develop HCC

Treatment:

  • Combination of IFN-alpha and ribavirin (more effective together than IFN-alpha alone)
  • New drugs: target viral protease; have been shown to have 70-80% cure rate
36
Q

HEPATITIS A VIRUS (HAV)

One of the most common causes of what?
How many serotypes?
Stability:
Can be inactivated by (3):

A

One of the most common causes of infectious jaundice in the world

Only 1 serotype (therefore, effective vaccine exists)

Very Stable: like other picornaviruses

  • Stable at 60 degrees C for one hour
  • Stable for years in the freezer
  • Withstands acid pH

However, can be inactivated by:
o Boiling
o Formalin (3 days)
o Chlorine (30 minutes)

37
Q 
HEPATITIS A VIRUS (HAV)
Replication
Where initially?
Spreads to:
Lymphoid cell infiltration: 
Excretion
A

Initial: in the intestinal mucosa

  • Spread to the liver: follows initial replication
  • Lymphoid cell infiltration: follows spread to the liver
  • Excreted in large amounts in the feces
38
Q

HEPATITIS A VIRUS (HAV)

Incubation period:
Prevention:

A

Incubation period: ~1 month

Prevention: inactivated vaccine (Havrix)

39
Q

HEPATITIS E VIRUS (HEV)

Family:
Found in what region of the world?
Who has a higher mortality rate?
May be carried by:

Genome:

A

Hepevirus family

  • Most commonly found in developing countries where the water supply is contaminated with fecal matter
  • Pregnant women have a higher mortality rate (~20%)
  • May be carried by wild rats

Genome: +ssRNA

40
Q

HEPATITIS F AND G VIRUSES:

Family:
Role in hepatitis:
HGV and HIV Progression:

A

Flaviviruses

  • Have been described, but play an uncertain role in causing hepatitis
  • ~5-10% of hepatitis cases known to be transmitted by blood transfusion cannot be attributed to a known virus (HFV/HFG?)

HGV and HIV Progression: co-infection with HGV in HIV patients slows the progression of HIV and prolongs the survival of AIDS patients

Micro Exam 2 (18 decks)

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