Viral replication and pathogenesis

Viral Replication: Dr Jawad Kadhum Al-Khafaji
-----------------------------------------------------------------------------------------

• Two phases in typical viral life cycle: intracellular and extracellular phases. In intracellular phase(inside host cell), the virus is active whereas, in extracellular phase(outside the living cells), the virus is inactive(inert metabolically).
• Viruses replicate only within living host cell, therefore they are known as obligate intracellular parasites, because lack necessary enzymes for synthesis of proteins and nucleic acid, so entirely dependent up on host cell energy for synthesis of macromolecules.
Stages of viral replication(life cycle of virus) involve the following events:
1. Attachment to host cell :
The first step in viral infection is attachment of virus to specific receptor on the surface of host cell.
• Receptor molecules differ for different viruses . For example, HIV attach to CD4 receptor on helper T-cell , and Rabies virus binds to acetylcholine receptor.
• The attachment of virus determine the organ specificity such as hepatitis virus infect liver, influenza virus infect respiratory tract , and so on.
• The specificity of attachment determines the host range of viruses and organ type. Some viruses have a narrow range , whereas others have a broad ranged.
2. Penetration :
Virus entry into host cell occurs through one of the following ways:
• Translocation of virion across plasma membrane .
• Endocytosis , in which the virus is accumulated inside cytoplasmic vacuole, then viral particle is taken up inside the cell.
• Fusion , the virus fuses with plasma membrane and enter into host cell .
3. Uncoating :
After engulf the virus in vesicle , within which the process of uncoating begins. Uncoating is removing the capsid proteins . Uncoating may be occur in cytoplasm or in nucleus. A low pH within the vesicle and presence of cellular enzymes which lead to dissolve the proteins of capsid, then result in uncoating and release of viral nucleic acid into infected host cell . The viral nucleic acid may remain in cytoplasm or migrate to nucleus.

4. Gene expression and biosynthesis:
Viruses can not replicate by binary fission or mitosis, but they replicate by complex process. When the viral genome released inside living host cell ,the virus is control on host cell biosynthesis , inhibition of macromolecules synthesis and use the energy of host cell in synthesis of viral macromolecules.
The gene expression involves :
• Replication of viral genome(synthesis of viral nucleic acids).
The DNA viruses replicate in nucleus (except poxviruses in cytoplasm), whereas the RNA viruses are replicate in the cytoplasm (except retroviruses and influenza virus in nucleus).
• Transcription of viral mRNA: synthesis of mRNA in viruses in various pathways : transfer of genetic information from parental genome to mRNA is called transcription.
• Translation of mRNA(synthesis of viral proteins) : Once the mRNA of either DNA viruses or RNA viruses is synthesized, and it translated by ribosome of host cell into viral proteins.

5. Assembly :
The virus produces many copies of their nucleic acid and proteins. The newly synthesized viral genome and structural proteins are assembling to form many progeny viruses.
The packaging of viral nucleic acid into capsid is occurring either in cytoplasm or in nucleus of infected cell .

6. Release :
The virus mature particles are released from the infected cell by one of two processes:
• Lyses of infected cell.
• Budding (without lysis) through the outer cell membrane .
Some viruses are enveloped , they acquire their envelops from cell membrane during releasing ,while other enveloped viruses acquire their envelop from nuclear membrane of infected cell.

Note:
• One virus produce many copies of their nucleic acid and proteins, and then reassemble into multiple progeny viruses lead to release hundreds of progeny (new)viruses from infected cell .