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Virus

Hepatitis A Virus
(Picornaviridae)

Hepatitis B Virus
(Hepadnaviridae)

MISCELLANEOUS VIRUSES
Characteristics
Icosahedral
Non-enveloped
SS+ nonsegmented
One serotype

Icosahedral
Enveloped
Double stranded
circular
Reverse
Transcriptase

Hepatitis C Virus

Helical
SS+ nonsegmented

Hepatitis D Virus

Circular
SSDefective virus
Requires HBV

(Flaviviridae)

Epidemiology
Spread: feco-oral
Location: hepatocyte
Risk Factors:
1. Undercooked
shellfish
2. Developing
countries
3. Poor sanitation
At Risk:
1. Unimmunized
children and adults
2. Travellers to
developing
countries
Spread: sexual,
blood
Location: body fluids
hepatocyte
Risk Factors:
1. Contaminated
needles
2. Multiple sex
partners
At Risk:
1. Babies with
infected mothers
2. IV drug users
3. Hemophiliacs
**Dane particle: 42
nm
Similar to HBV
Risk Factors:
1. Blood transfusion
2. Tattooing
Similar to HBV;
Sexually: not
transmitted as
frequently

Pathogenesis and Virulence


Pathogenesis
1. Oral infection passes intestines
2. Viremia: spread to blood
3. Infects hepatocytes: severe
cytopathology impairs liver
function

Diseases
Acute Hepatitis
1. Incubation period
2. Icteric phase: jaundice,
fever, fatigue, nausea, dark
amber urine, clay colored feces

1
Lab Diagnosis
ELISA: Anti-HAV antibodies

Treatment
>99% selflimiting
Killed HAV
vaccine

Serology
HBeAg: 1st to appear, 1st to
decline; highly infectious
HBsAg: 1st to appear,
disappearance leads to
window period, presence
signifies infection
HBcAg: not released in
blood, remains in
hepatocytes
Anti-HBcAg Ab: first to
appear
Anti-HBeAg Ab: 2nd Ab
Anti-HBsAg Ab:
protective Ab; virus is
eradicated from
patient; vaccination
Serology: HCV Ag
Increased liver enzymes

HBIg within a
week of
infection
PEGylated IFN: enhance
effectivity

Serology: IgM vs. delta Ag

Treat underlying
HBV

**NO CHRONIC!!

Pathogenesis
1. Viremia: spread to blood
2. Replicate in hepatocytes: reverse
transcriptase
3. Infects hepatocytes: express
nucleocapsid proteins (HBcAg &
HBeAg)
4. Hepatic cell destruction:
inflammation, necrosis
5. CTL killing, NK cells and IFN-:
limit infection
6. Anti-HBsAg Ab neutralizes the
remaining free viruses

Acute Hepatitis!!
1. Pre-icteric phase: mild fever,
malaise, anorexia, myalgia
2. Icteric phase: jaundice,
fever, fatigue, nausea, dark
amber urine, clay colored
feces
Chronic Hepatitis
1. Hepatic cell carcinoma
2. Liver cirrhosis
3. Extrahepatic disease:
hepatic encephalopathy

Virulence
1. Resistant to low pH
Similar to HBV

1. Delta antigen: complexed with


RNA genome
2. Uses HBV and target cell protein
for replication
3. HBsAg: essential for viral
packaging of HDV

1. Acute Hepatitis (25% of


infected individuals
2. Chronic Hepatitis: HIGH
chance of progression;
chronic fatigue; candidate for
liver transplant
Fulminant Hepatitis: Severe
form of acute hepatitis (HBV);
increase mortality rates,
increased likelihood for
cirrhosis, HCC, death
Chronic Hepatitis: primary
HDV infection of chronically
HBV infected individual;
increase chances of fulminant
hepatitis

No vaccine
IFN-
Combination
therapy: IFN-
and ribavirin

MISCELLANEOUS VIRUSES

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Hepatitis E
Virus
(Caliciviridae)

Hepatitis G Virus
(Flaviviridae)

Human
Immunodeficiency
Virus
(Retroviridae)

Icosahedral
Non-enveloped
SS+ nonsegmented

Helical
SS+ nonsegmented
Icosahedral
Enveloped
SS+ diploid
Reverse
Transcriptase
Genes:
1. gag: nuclear import
2. pol: polymerase
3. env: envelope
(gp120 and gp41)
Proteins:
1. gp120: attachment
2. gp41:
transmembrane
3. p17: matrix
4. p24: capsid; first
Ag, first Ab
5. Protease: uncoat
6. Reverse
Transcriptase: RNA
to DNA
7. Integrase:
incorporates viral
DNA to nucleus

Human T
Lymphocyte Virus
(Retroviridae)

Icosahedral
Enveloped
SS+ diploid
Reverse
Transcriptase

Spread: feco-oral
Location: hepatocyte
Risk Factors:
1. Developing
countries
At Risk:
1. Pregnant
women
2. Young adults
Similar to HCV

Similar to HAV

Similar to HCV

Spread: sexual
contact, transfusion,
contaminated
needles, perinatal
Location: CD4+ T
cells and
macrophages
Risk Factors:
1. Developing
countries
2. Homosexual
intercourse
At Risk:
1. Homosexuals
2. IV drug users

Pathogenesis
1. HIV initially infects macrophages
in genital tract
2. Macrophages & DC present HIV
to CD4+ T cells in lymph nodes
3. Acute phase viremia: high level
of virus replication in CD4+;
similar to infectious
mononucleosis
4. Latent period: acute phase
viremia is reduced by HIV-specific
CTL
5. Progression to AIDS: any T
cell stimulation (infection) will
lead to HIV replication
depletion of CD4+ counts
6. Full Blown AIDS: depleted
CD4+ count; myriad of
opportunistic diseases; spread to
many organs

Spread: sexually,
blood, placental
Location: T cells
Risk Factors:
1. Endemic areas

Acute Hepatitis
1. Incubation period
2. Icteric phase: jaundice,
fever, fatigue, nausea, dark
amber urine, clay colored feces

2
RT-PCR
Serology: Ab vs. HEV Ag

No vaccine

Similar to HCV

RT-PCR
Serology: Ab vs. HGV Ag

IFN-

Acute Phase Viremia:


occurs during initial infection;
mononucleosis-like
symptoms

Serology: Anti-HIV Ab
1. Screening: ELISA
2. Confirm: Western Blot
detect one gag, pol and env
protein
Flow Cytometry: low
CD4+:CD8+ ratio

RT inhibitors:
AZT
Protease inh:
vir drugs
HAART:
combination
therapy (1
prot, 2 RT
inh)
Prophylactic:
Truvada

**NO CHRONIC!!

Virulence
1. Highly mutable, great
antigenic variability: no vaccine
2. Lytic infection of CD4+ T cells
3. Syncytia formation: cell-cell
spread
4. Reservoir: CD4+ T cells and
macrophages
5. Decreased CD8+, macrophage
and non-specific Ab production
Immortalization of T cells (HTLV-1:
CD4+; HTLV-2: CD8+)

AIDS-Related Complex
(CD4+ >500/uL)
1. Lymphadenopathy
2. Fever, weight loss, diarrhea,
malaise
3. Listeriosis
4. Oral thrush
5. Hairy Leukoplakia

**Window period: First 24 weeks no HIV Ab; test


for p24!

Full Blown AIDS


(CD4+ >200/uL)
1. AIDS-related Dementia: slow
deterioration of intellect
2. Bacterial infections: M. avium
intracellulare, tuberculosis,
salmonella septicemia
3. Viral infections: CMV, HSV,
JC
4. Protozoal infections:
Cryptosporidium, Toxoplasma

Mostly asymptomatic
1. Adult T-cell Leukemia:
malignancy of T cells; impaired
immune system; opportunistic
infections
2. Uveitis and Retinal vasculitis

Serology: Anti-HTLV-1 Ab

None
Chemotherapy
is ineffective

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