Aids byname and acronym of acquired immunodeficiency syndrome

Life cycle of HIV

T cell infected with HIV
The main cellular target of HIV is a special class of white blood cells critical to the immune system known as helper T lymphocytes, or helper T cells. Helper T cells are also called CD4+ T cells, because they have on their surfaces a protein called CD4. Helper T cells play a central role in normal immune responses by producing factors that activate virtually all the other immune system cells. Those include B lymphocytes, which produce antibodies needed to fight infection; cytotoxic T lymphocytes, which kill cells infected with a virus; and macrophages and other effector cells, which attack invading pathogens. AIDS results from the loss of most of the helper T cells in the body.
HIV is a retrovirus, one of a unique family of viruses that consist of genetic material in the form of RNA (instead of DNA) surrounded by a lipoprotein envelope. HIV cannot replicate on its own and instead relies on the mechanisms of the host cell to produce new viral particles. HIV infects helper T cells by means of a protein embedded in its envelope called gp120. The gp120 protein binds to a molecule called CD4 on the surface of the helper T cell, an event that initiates a complex set of reactions that allow the HIV genetic information into the cell.
Entry of HIV into the host cell also requires the participation of a set of cell-surface proteins that normally serve as receptors for chemokines (hormonelike mediators that attract immune system cells to particular sites in the body). Those receptors, which occur on T cells, are often described as coreceptors, since they work in tandem with CD4 to permit HIV entry into the cells. Chemokine receptors that are known to act as HIV coreceptors include CCR5 (chemokine [C-C motif] receptor 5) and CXCR4 (chemokine [C-X-C motif] receptor 4), both of which are classified as G protein-coupled receptors. The binding of gp120 to CD4 exposes a region of gp120 that interacts with the chemokine receptors. That interaction triggers a conformational change that exposes a region of the viral envelope protein gp41, which inserts itself into the membrane of the host cell so that it bridges the viral envelope and the cell membrane. An additional conformational change in gp41 pulls those two membranes together, allowing fusion to occur. After fusion the viral genetic information can enter the host cell. Both CCR5 and CXCR4 have generated significant interest as targets for drug development; agents that bind to and block those receptors could inhibit HIV entry into cells.
Once the virus has infected a T cell, HIV copies its RNA into a double-stranded DNA copy by means of the viral enzyme reverse transcriptase; that process is called reverse transcription, because it violates the usual way in which genetic information is transcribed. Because reverse transcriptase lacks the “proofreading” function that most DNA-synthesizing enzymes have, many mutations arise as the virus replicates, further hindering the ability of the immune system to combat the virus. Those mutations allow the virus to evolve very rapidly, approximately one million times faster than the human genome evolves. That rapid evolution allows the virus to escape from antiviral immune responses and antiretroviral drugs. The next step in the virus life cycle is the integration of the viral genome into the host cell DNA. Integration occurs at essentially any accessible site in the host genome and results in the permanent acquisition of viral genes by the host cell. Under appropriate conditions those genes are transcribed into viral RNA molecules. Some viral RNA molecules are incorporated into new virus particles, whereas others are used as messenger RNA for the production of new viral proteins. Viral proteins assemble at the plasma membrane together with the genomic viral RNA to form a virus particle that buds from the surface of the infected cell, taking with it some of the host cell membrane that serves as the viral envelope. Embedded in that envelope are the gp120/gp41 complexes that allow attachment of the helper T cells in the next round of infection. Most infected cells die quickly (in about one day). The number of helper T cells that are lost through direct infection or other mechanisms exceeds the number of new cells produced by the immune system, eventually resulting in a decline in the number of helper T cells. Physicians follow the course of the disease by determining the number of helper T cells (CD4+ cells) in the blood. That measurement, called the CD4 count, provides a good indication of the status of the immune system. Physicians also measure the amount of virus in the bloodstream—i.e., the viral load—which provides an indication of how fast the virus is replicating and destroying helper T cells.