Reverse transcription

Reverse transcription

In the cytoplasm of the cell, HIV reverse transcriptase converts viral RNA into DNA, the nucleic acid form in which the cell carries its genes. Fifteen of the 26 antiviral drugs approved in the United States for treating people with HIV infection work by interfering with this stage of the viral life cycle.

Integration

The newly made HIV DNA moves to the cell's nucleus, where it is spliced into the host's DNA with the help of HIV integrase. HIV DNA that enters the DNA of the cell is called a provirus. Several drugs that target the integrase enzyme are in the early stages of development and are being investigated for their potential as antiretroviral agents.

Transcription

For a provirus to produce new viruses, RNA copies must be made that can be read by the host cell's protein-making machinery. These copies are called messenger RNA (mRNA), and production of mRNA is called transcription, a process that involves the host cell's own enzymes. Viral genes in concert with the cellular machinery control this process; the tat gene, for example, encodes a protein that accelerates transcription. Genomic RNA is also transcribed for later incorporation in the budding virion (see below).

Cytokines, proteins involved in the normal regulation of the immune response, also may regulate transcription. Molecules such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, secreted in elevated levels by the cells of HIV-infected people, may help to activate HIV proviruses. Other infections, by organisms such as Mycobacterium tuberculosis, also may enhance transcription by inducing the secretion of cytokines.

Translation

After HIV mRNA is processed in the cell's nucleus, it is transported to the cytoplasm. HIV proteins are critical to this process; for example, a protein encoded by the rev gene allows mRNA encoding HIV structural proteins to be transferred from the nucleus to the cytoplasm. Without the rev protein, structural proteins are not made. In the cytoplasm, the virus co-opts the cell's protein-making machinery-including structures called ribosomes-to make long chains of viral proteins and enzymes, using HIV mRNA as a template. This process is called translation.