Hepatitis C Virus

By. Febby E. Kandou

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 • Hepatitis C is a blood-borne, infectious,
viral disease that is caused by a
hepatotropic virus called Hepatitis C Virus
(HCV)
• The infection can cause liver inflammation
(hepatitis), often asymptomatic
• Hepatitis chronic: cirrhosis and liver
cancer

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 Chronic HCV Liver Disease Cells

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 Liver Cirrhosis

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 History
• In the mid 1970s, this virus called
Non-A, Non-B Hepatitis (NANBH)
• In April of 1989, re-named Hepatitis C
Virus (HCV)

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 Classification
• Group : Group IV (+)ssRNA
• Family : Flaviviridae
• Genus : Hepacivirus
• Spesies : Hepatitis C Virus

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 Structure
• Small, 50 nm in size
• Enveloped, single-stranded, positive
sense RNA ((+)ssRNA)
• Genom encodes 10 protein,
including 2 glycoproteins, E1 and E2

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 • Two HCV receptors: The tetraspanin
CD81 and the human scavenger
receptor class B1 (SR-BI)

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 Replication
• HCV has a high rate of replication
with approximately one trillion
particles produced each day in an
infected individual
• Location replication: HCV replicates
within hepatocytes in the liver (in the
cytoplasm and remains in the ER)

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 HCV Life Cycle
• HCV particles bind to receptors on the
surfaces of hepatocytes and enter the
cells (HCV receptors are CD81 and
scavenger reseptor class B1)
• Fusion and uncoating
• HCV genome is translated to produce a
single protein of around 3011 amino acids.
– This “polyprotein” is then proteolytically
processed by viral and cellular proteases to
produce 3 structural (virion-associated) and 7
non-structural (NS) proteins
– HCV encodes 2 proteases: NS2 cysteine auto
protease and NS3-4A serine protease
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 • NS proteins then recruit the viral genome
into an RNA replication complex
• RNA replication takes places via the viral
RNA-dependent RNA polymerase of NS5B,
which produces a negative-strand RNA
intermediate
• The negative strand RNA then serves as a
template for the production of new
positive-strand viral genomes

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 • Nascent genomes can then be
translated, further replicated, or
packaged within new virus particles
• New virus particles presumably bud
into the secretory pathway and are
released at the cell surface

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 •
• Virus binding and internalization (a); cytoplasmic release
and uncoating (b); IRES-mediated translation and
polyprotein processing (c); RNA replication (d); packaging
and assembly (e); virion maturation and release (f). The
topology of HCV structural and non-structural proteins at
the endoplasmic reticulum membrane is shown
schematically. HCV RNA replication occurs in a specific
membrane alteration, the membranous web. Note that
IRES-mediated translation and polyprotein processing, as
well as membranous web formation and RNA replication,
which are illustrated here as separate steps for simplicity,
might occur in a tightly coupled fashion. IRES, internal
ribosome entry site.

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 • HCV Life Cycle (clockwise from top left):
The HCV life cycle presents a variety of accessible targets with
potential therapeutic utility. Initially, the HCV virus recognizes and
is incorporated into human liver cells. The internalized virus then
dissociates, liberating the viral RNA genome. The HCV RNA is
then translated by the host ribosomes, producing the HCV
polypeptide. This polypeptide is subsequently processed, first by
host peptidases then by the HCV proteases (NS2 and NS3) into 10
different HCV proteins. The non-structural proteins (NS2-NS5b)
are next assembled and localized within the liver cell to form a
replication complex which produces multiple copies of the HCV
RNA genome. These RNA copies are then able to reenter the life
cycle, producing more HCV proteins. Eventually, the HCV
structural proteins (C, E1 and E2) along with copies of the HCV
RNA are packaged as infectious virus particles, released from the
liver cell, and are able to infect new cells.

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• Hypothetical model of HCV replication complex

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• Localization of HCV proteins

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 • a | Low-power overview of a Huh-7 cell harbouring a
subgenomic HCV replicon. A distinct membrane alteration,
named the membranous web (arrows), is found in the
juxtanuclear region of the cell. Note the circumscript nature
of this specific membrane alteration and the otherwise
unaltered cellular organelles. Scale bar represents 1 m. b |
Higher magnification of a membranous web (arrows), which
is composed of small vesicles that are embedded in a
membrane matrix. Note the close association of the
membranous web with the rough endoplasmic reticulum.
Scale bar represents 500 nm. The membranous web
contains all HCV non-structural proteins and nascent viral
RNA in Huh-7 cells that harbour subgenomic replicons114,
and therefore represents the subcellular site of HCV RNA
replication. ER, endoplasmic reticulum; M, mitochondria; N,
nucleus.

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 Transmission
• HCV is transmitted by blood-to-blood contact
• Methods of transmission, several activities have
been identified as potential sources of exposure
to HCV:
– Injection drug use
– Drug use by nasal inhalation
– Blood products
– Recreational exposure to blood
– Sexual exposure to blood
– Body piercing and tattoo
HCV is not spread→casual contact such as hugging,
kissing, or sharing eating or cooking utensils

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 Transmission

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 Diagnosis
• ELISA antibody testing for
immunocompetent
• Seroconversion within 7-31 weeks of
initial infection
• Testing for immunocompromised
and hemodialysis recipient:
– Reverse transcriptase PCR
– Branched-chain DNA

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 Treatment
• Very small chance of clearing the virus
spontaneously (0,5 to 0,74% per year)
• The majority of patient with chronic
hepatitis C will not clear it without
treatment
• Current treatment→combination of
pegylated interferon alpha (brand names
Pegasys and PEG-Intron and antiviral drug
Ribavirin for a periode of 24 or 48 weeks,
depending on genotype

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 Interferon and Hepatitis C

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 Vaccination
• Unlike Hepatitis A and B, there is no
vaccine to prevent hepatitis C
infection

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 Prevention
• Avoid sharing drug needles
• Avoid unsanitary tattoo methods
• Avoid unsanitary body piercing
methods and acupunture
• Avoid needlestick injury
• Avoid sharing personal items such
as toothbrusher, razors, and nail
clippers

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