How HIV makes people sick

HIV binds to T-cell and empties its components inside

Although HIV can infect a number of cells in the body, its main targets are T-cells called CD4 positive (CD4+) cells. T-cells are a kind of lymphocyte, which are cells that the body's immune system makes to fight off dangerous invaders. (Lymphocytes are also called white blood cells.) T-cells that have a molecule called cluster designation 4 (CD4) on their surfaces are called CD4+, or T-helper cells.

To bind to the CD4+ cell, a molecule on the cap of an HIV spike first forms a chemical bond with a CD4 molecule on the host cell's surface. The molecule then binds to another receptor on the host cell's surface, such as CCR5 or CXCR4. HIV's viral envelope and the host cell's membrane then fuse together, allowing the virus to empty its contents into the cell.

HIV changes to enter the cell's nucleus

In most cells and normal viruses, DNA is first converted to RNA in a process called transcription, and then RNA is turned into proteins in a process called translation. HIV is different, though, and must first convert its RNA into DNA in a process called reverse transcription. For reverse transcription, HIV uses an enzyme called reverse transcriptase. The viral DNA that results from reverse transcription contains the instructions HIV needs to hijack a T-cell's genetic machinery and begin reproducing itself (Pieribone, 2002/2003).

Some of the drugs approved in the United States for the treatment of people infected with HIV work by interfering with reverse transcriptase's ability to change RNA to DNA. These drugs are called reverse transcriptase inhibitors.

HIV DNA splices with host DNA and begins to copy itself

The newly reverse-transcripted HIV DNA next makes its way into the host cell's nucleus. Once inside, the HIV DNA is spliced into strands of the host cell DNA, with the aid of an enzyme called integrase. This process is called integration (Pieribone, 2002/2003). HIV DNA that enters the host cell DNA is called a provirus.

In order to survive, the HIV provirus must eventually make copies of itself, or replicate. The first step to replication is a process called transcription. Transcription creates a strand of genetic code that the host cell's protein-making machinery can read. During transcription, an enzyme called RNA polymerase separates the two halves of DNA like a zipper. One of these halves is then used to create a new strand of RNA, called messenger RNA (mRNA). HIV's genes may actually accelerate the process of transcription.

During translation, structures in the host cell's cytoplasm (that is, the area outside of the nucleus) use the mRNA as a blueprint for building proteins and enzymes. These new proteins and enzymes will eventually come together to make a new HIV particle.

Immature virus forms, pushes out from cell, and becomes infectious

The newly made proteins and enzymes, as well as viral RNA, come together just inside the host cell's membrane. Proteins, enzymes, and RNA form a bud on the surface of the host cell membrane. As the viral particle pushes off from the infected host cell, it takes proteins from the host cell membrane that will become the particle's viral envelope. The core of the virus is still immature, so the HIV particle cannot yet infect other host cells.

At the last step of the viral cycle, a viral enzyme called protease cuts the long chains of proteins and enzymes in the HIV particle core, making the particle infectious. At this stage, the HIV particle is said to be mature. Drugs called protease inhibitors interfere with this last step of the viral life cycle (Pieribone, 2002/2003).