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Hepatitis C

> 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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