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The Hepatitis C virus (HCV) is a small (50 nm in size), enveloped,
single-stranded, positive sense RNA
virus. It is the only known member of the hepacivirus genus in the
family Flaviviridae. There are six major genotypes
of the hepatitis C virus, which are indicated numerically (e.g.,
genotype 1, genotype 2, etc.). This virus causes
a blood-borne infectious disease Hepatitis C infecting
the liver. The infection can cause liver inflammation
(hepatitis) that is often asymptomatic, but ensuing
chronic hepatitis can result later in cirrhosis (fibrotic scarring
of the liver) and liver cancer.
Virus
classification-
Group: Group IV ((+)ssRNA)
Family: Flavivirida
Genus: Hepacivirus
Structure-
> The structure of the hepatitis C virus consists of a core of
genetic material (RNA), surrounded by an
icosahedral protective shell of protein, and further encased in
a lipid (fatty) envelope of cellular origin. Two
viral envelope glycoproteins, E1 and E2, are embedded in the lipid
envelope.
Mechanism
of action-
> HCV presumably binds to specific receptor(s) and enters cells
through endocytosis, as do other members of Flaviviridae.
> The viral genome is translated into a precursor polyprotein
after uncoating, and viral RNA is synthesized
by a virus-encoded polymerase complex.
> Progeny
viral particles are released into the luminal side of the endoplasmic
reticulum and secreted from the cell after passage
through the Golgi apparatus.
Genome-
>
Hepatitis C virus has a positive sense RNA genome that consists
of a single open reading frame of 9600 nucleoside
bases.Genome is enveloped in a lipid bilayer in which two or more
envelop proteins (E) are anchored.The envelop
surrounds the nucleocapsid, which is composed of multiple
copies of a small basic protein (core or C),and contains the RNA
genome.
> The HCVpolyprotein is cleaved co- and post-translationally
by cellular and viral proteases into ten different
products, with the structural proteins [core (C), E1 and E2] located
in the N- terminal third and the nonstructural
(NS2-5) replicative proteins in the remainder.
Replication/Life
Cycle-
> HCV mainly replicates within hepatocytes in the liver.
> Replication of HCV involves several steps:
1. Binding of HCV to a cell surface receptor
complex-
> Circulating HCV particles bind to receptors
on the surfaces of hepatocytes and subsequently
enter the cells.
2. The virus (or at least its genetic information)
penetrates the plasma
Membrane and enters the cell.
3.
Cytoplasmatic release and uncoding of viral genome-
>
It utilizes the intracellular machinery necessary to accomplish
its own replication.
> The
HCV genome is translated to produce a single protein. This "polyprotein"
is then proteolytically processed
by viral and cellular proteases to produce three structural (virion- associated)
and seven nonstructural (NS) proteins.
4. RNA Replication-
> The NS proteins then recruit the viral genome
into an RNA replication complex, which is associated
with rearranged cytoplasmic membranes.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.These genomes can then be translated, further replicated,
or packaged within new virus
particles.New virus particles through the secretory pathway are
released at the cell surface.
Genotypes-
> Based on genetic differences between HCV isolates, the hepatitis
C virus species is classified into six genotypes
(1-6) with several subtypes within each genotype (represented by
letters).Subtypes are further broken down into
quasispecies based on their genetic diversity.
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