Thursday, 29 November 2007

The AIDS Process in Body

Attachment to the Lymphocyte Membrane
On the surface membrane of all living cells are complex protein structures called "receptors". A receptor is often compared to a lock into which a specific key or "ligand" will fit. There are at least two receptors on T-lymphocytes to which the human immunodeficiency virus (HIV) sticks. The primary receptor, called "CD4", is shown on the right in the diagram. But a second receptor that loops through the cell membrane 7 times is critical for infection to occur.

HIV infection of a lymphocyte requires attachment of the virus to the cell membrane through both of these "ligand-receptor" links. In cells whose "7-transmembrane receptor" is different, the HIV "key" no longer matches the lymphocyte "lock" and attachment is incomplete. Those cells may avoid infection by HIV.

Entry of the Viral RNA
Tight attachment of the viral particle to receptors on the lymphocyte membrane enables fusion with the cell membrane. The viral contents, including viral RNA (shown in yellow) then empty into the cell's cytoplasm.

Like other viruses that infect human cells, HIV commandeers the host's machinery to make multiple copies of itself.

Reverse Transcription: Converting viral RNA into DNA
Viral RNA (yellow)
DNA (blue)


An enzyme (protein) that's part of the human immunodeficiency virus reads the sequence of viral RNA nucleic acids that have entered the host cell and transcribes the sequence into a complementary DNA sequence. That enzyme is called "reverse transcriptase" . Without reverse transcriptase, the viral genome couldn't become incorporated into the host cell, and couldn't reproduce.

Reverse transcriptase sometimes makes mistakes reading the RNA sequence. The result is that not all viruses produced in a single infected cell are alike. Instead, they end up with a variety of subtle molecular differences in their surface coat and enzymes. Vaccines, which induce the production of antibodies that recognize and binding to very specific viral surface molecules, are an unlikely player in fighting HIV, because throughout infection, HIV surface molecules are continually changing.

Integration of Viral DNA
Once the viral RNA has been reverse-transcribed into a strand of DNA, the DNA can then be integrated (inserted) into the DNA of the lymphocyte. The virus has its own enzyme called "integrase" that facilitates incorporation of the viral DNA into the host cells DNA. The integrated DNA is called a provirus.

Transcription: Back to RNA
As long as the lymphocyte is not activated or "turned-on", nothing happens to the viral DNA. But if the lymphocyte is activated, transcription of the viral DNA begins, resulting in the production of multiple copies of viral RNA. This RNA codes for the production of the viral proteins and enzymes (translation) and will also be packaged later as new viruses.

Translation: RNA to ProteinsThere are only 9 genes in the HIV RNA. Those genes have the code necessary to produce structural proteins such as the viral envelope and core plus enzymes like reverse transcriptase, integrase, and a crucial enzyme called a protease.

Viral Protease

When viral RNA is translated into a polypeptide sequence, that sequence is assembled in a long chain that includes several individual proteins (reverse transcriptase, protease, integrase). Before these enzymes become functional, they must be cut from the longer polypeptide chain. Viral protease cuts the long chain into its individual enzyme components which then facilitate the production of new viruses.

Assembly and Budding

Finally, viral RNA and associated proteins are packaged and released from the lymphocyte surface, taking with them a swatch of lymphocyte membrane containing viral surface proteins. These proteins will then bind to the receptors on other immune cells facilitating continued infection.

Budding viruses are often exactly like the original particle that initially infected the host. In the case of HIV, however, the resulting viruses exhibit a range of variations which makes treatment difficult.



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