Hepatitis C Virus (HCV)                                                                    

 

Structure of The Virus                                                                 

The hepatitis C virus (HCV) is a positive-sense single-stranded RNA virus. It has the same structure as messenger RNA (mRNA) which means it can be translated (in a 5’ to 3’ direction), directly into viral proteins inside a host cell without any alterations. The genetic material however can be carried in a variety of forms, depending on the virus. 

 

The virus itself is composed of an RNA core, which is surrounded by an icosahedral protective shell of protein called the capsid. The viral genome together with the capsid is called a nucleocapsid; this is enveloped in a lipid layer that is embedded with E1 and E2 glycoproteins, which allow for cellular interaction.

           

How the Virus Spreads

Viruses spread by infiltrating host cells and using their transcription machinery to replicate the viral genome, and synthesise viral proteins. All viral genomes encode three types of proteins: 

  • Proteins for replicating the genome

  • Proteins for packaging the genome and delivering it to more host cells, either by bursting the host cell (cell lysis), or by utilising the host cell’s export mechanisms

  • Proteins that modify the structure of the host cell to enhance the replication of the viral genome

     

After the virus has recognised and attached to the host cell’s surface, it must enter the cell and release its viral genome from its protective protein capsid. Enveloped viruses like HCV enter the host cell by fusing with its plasma membrane and releasing their genome and capsid proteins into the cytoplasm.

 

Another mechanism involves the virus binding to cell surface receptors and causing receptor-mediated endocytosis; the envelope then fuses with the endosome membrane, causing the release of the viral genome and capsid proteins into the cytoplasm.

 Animation of viral infection of host cell

Figure 2.2

Animation Showing Infiltration and Replication of Virus Particles in Neighbouring Cells

 

Mechanism of Replication

HCV replicates predominantly in hepatocytes, which are cells found in liver tissue. It has been found that the virus can also replicate in peripheral blood mononuclear cells (cells in the blood that have a round nucleus e.g. white blood cells), which explains why high levels of immunological disorders are typically found in chronically infected HCV patients.

 

HCV is classified into six different genotypes, all of which mutate rapidly due to the high rate of errors produced by RNA-dependent RNA polymerase, during the transcription of the viral RNA. It produces so many different variants of the virus, that HCV is considered to be a quasispecies rather than a normal species, whose progeny inherit a normal stable genotype.

 

Once the HCV has infiltrated a hepatocyte cell, it takes over the intracellular machinery, so it can replicate and spread. The genome is translated into structural and non-structural proteins that are replicated by RNA-dependent RNA polymerase, which produces a negative strand RNA intermediate. This then serves as a template for new positive-sense viral RNA strands that are then packaged into new virus particles, to be exported into neighbouring cells.

HCV replication

Figure 2.3 

Shows the Infiltration, Replication and Transmission Mechanisms of the Hepatitis C Virus (HCV) inside a cell

Pathogenesis

Hepatitis C primarily affects the hepatocytes of the liver and sometimes white blood cells present in the blood, causing immunological disorders and liver damage. Chronic infection can decrease liver function which can lead to increased pressure in the liver circulation, causing portal vein hypertension. Loss of liver function can also lead to liver fibrosis which is characterised by varices (enlarged veins), jaundice, bruising and bleeding. Severe liver damage can eventually lead to hepatocellular carcinoma (HCC).

 

Many symptoms suggestive of liver disease are normally absent until extensive liver scarring has occurred. Furthermore, hepatitis C infection rarely expresses any symptoms and if it does, they are typically vague and non-specific. 

 

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