Retrovirus Cell Invasion

Viruses are small submicroscopic parasites that rely on their hosts for energy production, replication, and release to infect further cells. Since viruses lack the ability to produce ATP, entry into a living cell is a necessity for the use of the host cell's metabolic machinery for DNA, RNA, and protein synthesis. The type of cell or tissues that a virus can infect is called the virus' host range. An example of virus with a very narrow host rage would be Human Papilloma virus (HPV), which can only infect human epithelial cells while herpes simplex virus (HSV) has a broad range and is able to infect multiple cell and tissue types. For further information on virus classifications and host ranges please look at the following site:




Necessary Steps for Cell Invasion

Cell Recognition

The first step in cell invasion is recognition of the Host's cell through surface receptors located on the cell's surface. Viruses will either use a receptor that is found on many cells (such as sialic-acid-containing oligosaccharides, which are used by the influenza virus) or one that is found only on the surface of the type of cell that is needed for replication (such as the nicotinic acetylcholine receptor or the cell-cell adhesion protein N-CAM which are used by the rabies virus). Some viruses such as HIV require a co-receptor also be present. HIVs primary receptor is the CD4 receptor found on the surface of T-cells and macrophages and the co-receptor CCR5. Recently a mutated strain also uses the CXCR4 receptor as its co-receptor. Once the correct receptor is found, the virus will attach to the cell surface.




Receptor mediated endocytosis

In most enveloped viruses, receptor mediated endocytosis is followed by an uncoating of the viral envelope to expose the DNA/RNA core. This step is accomplished as the environment in the newly formed endosome becomes acidic. The acidic environment causes conformational changes in the viral envelope and fusion with the endosomal membrane. The fusion of the viraland endocytic membranes allows for the release of the viral genome into the cytosol.




Fusion

Viruses such as HIV will fuse directly with the plasma membrane and release into the cytosol. This is accomplished as the CD4 and chemokine receptors interact releasing the anchoring protein Gp120. Once inserted into the plasma membrane, the anchoring proteins undergo changes facilitating fusion of the virus with the plasma membrane resulting in the release of the viral genome directly into the cytosol.




The picture below gives a comparison of different strategies used by viruses to invade the cell. Each is different but the end result is the same. Infection of the cell, with the genomic contents of the virus, where the business of replication begins.



References

Biology of Viruses (2006) [Online]
Molecular Biology of The Cell (2006) [Online]