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Saturday, January 30, 2010

Virus Replication Cycle Part II

3. UNCOATING
Uncoating is a process that viral capsid is degraded by viral enzymes or host enzymes (for e.g. lysozymes).


Uncoating in general refers to the events that expose the viral genome to the host cellular machinery and sets the stage for the viral genome to express its functions required for the replication.

This stage occurs simultaneously with or rapidly after penetration. In order to express the viral genome to the cell organelles, it is necessary that the virion coat be removed partially or completely. Therefore, once virions are in the cytoplasm, they are generally uncoated to some extent by a variety of processes, including simple dissociation and/or enzyme-mediated partial degradation of the particles, to release the viral genome as a naked nucleic acid or as a nucleoprotein complex.

The steps involved in the process of disintegration of the protein coat or capsid to release its genome into the cell is called as uncoating. Uncoating may be achieved by the complete or partial removal of the capsid.


Penetration and endosomal uncoating

Uncoating of adenovirus and influenza virus.
Uncoating of HIV virus and paramyxoviridae virus.

4. REPLICATION
Replication involves assembly of viral proteins and genetic materials produced in the host cell.

The viral genome directs the host cell's metabolic machinery (ribosomes, tRNA, nutrients, energy, enzymes, etc.) to synthesize viral enzymes and viral parts. The viral genome has to both replicate itself and become transcribed into viral mRNA molecules. The viral mRNA can then be translated by the host cell's ribosomes into viral structural components and enzymes need for replication and assembly of the virus.Viruses can store their genetic information in six different types of nucleic acid which are named based on how that nucleic acid eventually becomes transcribed to the viral mRNA:

As the host cell's ribosomes attach to the viral mRNA molecules, the mRNAs are translated into viral structural proteins and viral enzymes. During the early phase of replication, proteins needed for the replication of the viral genome are made and the genome makes thousands of replicas of itself. During the late phase of replication, viral structural proteins (capsid and matrix proteins, envelope glycoproteins, etc.) and the enzymes involved in maturation are produced. Some viruses translate mRNA molecules that are transcripts of several genes into one or more large polyproteins. These polyproteins are subsequently cut into individual functional proteins by viral enzymes called proteases. Other viruses produce monocistronic mRNA molecules, each coding for a separate functional protein.

In the case of most RNA viruses, replication and assembly occurs in the host cell's cytoplasm. With DNA viruses, most replication and assembly occurs in the nucleus of the host cell. The viral genome enters the nucleus of the host cell and here is transcribed into viral mRNA. The viral mRNA molecules then leave the nucleus through the pores in the nuclear membrane and are translated into viral proteins by the host cell's ribosomes in the cytoplasm. Most of these viral proteins then re-enter the nucleus where the virus assembles around the replicated genomes.
Also during replication, viral envelope proteins and glycoproteins coded by the viral genome are incorporated into the host cell's cytoplasmic membrane (see Fig. 11A and Fig. 11B) or nuclear membrane.

5. MATURATION
Maturation is the assembly of protein capsid.

During maturation, the capsid is assembled around the viral genome (A complete set of genes).


6. RELEASE
Viruses may escape from the host cell by causing cell rupture (lysis). Enveloped viruses (e.g., HIV) typically "bud" from the host cell.
During the budding process, a virus acquires the phospholipid envelope containing the embedded viral glycoproteins.

a. Naked viruses
Naked viruses are predominantly released by host cell lysis. While some viruses are cytolytic and lyse the host cell more or less directly, in many cases it is the body's immune defenses that lyse the infected cell.
b. Enveloped viruses
With enveloped viruses, the host cell may or may not be lysed. The viruses obtain their envelopes from host cell membranes by budding. As mentioned above, prior to budding, viral proteins and glycoproteins are incorporated into the host cell's membranes. During budding the host cell membrane with incorporated viral proteins and glycoproteins evaginates and pinches off to form the viral envelope. Budding occurs either at the outer cytoplasmic membrane, the nuclear membrane, or at the membranes of the Golgi apparatus
Viruses obtaining their envelope from the cytoplasmic membrane are released during the budding process.

Viruses obtaining their envelopes from the membranes of the nucleus, the endoplasmic reticulum, or the Golgi apparatus are then released by exocytosis(During exocytosis, a cell releases waste products or specific secretion products by the fusion of a vesicle with the cytoplasmic membrane) via transport vesicles.


Some viruses, capable of causing cell fusion, may be transported from one cell to adjacent cells without being released, that is, they are transmitted by cell-to-cell contact whereby an infected cell fuses with an uninfected cell.

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