The HIV life-cycle

Viruses are unable to replicate by themselves, and therefore must enter host cells and ‘hijack’ the cell’s protein-producing machinery.

Before they enter cells, HIV virus particles – known as ‘virions’ – are surrounded by an outer coat, or envelope. In order to enter a cell, proteins on the envelope must bind to CD4 receptors on the cell surface, as well as an additional co-receptor, either CCR5 or CXCR4. Once HIV has attached to both CD4 and one of the co-receptors, the virus envelope can fuse with the cell membrane, and thereby release the contents of the virion into the cell.

Virions contain several viral proteins plus HIV’s genetic material, or genome. The genetic material is enclosed within a structure called a nucleocapsid, which breaks apart early in the replication process. The HIV genome consists of nine genes: gag, pol, env, vif, vpu, CPR, tat, rev and nef. These genes carry all the information needed to make new viruses. One set of genes – gag, pol and env – are structural genes that govern the structure of the virus; gag and pol also give rise to three enzymes essential for HIV replication :

• Reverse transcriptase – needed to convert viral RNA to DNA.
• Integrase – enables HIV to insert its genetic material into the cell’s genome.
• Protease – cuts up newly produced viral proteins.

Viruses are classified based on whether their genetic material is made up of DNA (as with herpes viruses) or RNA (as with HIV and hepatitis C virus). Retroviruses are a subset of RNA viruses that replicate in a unique way by using reverse transcriptase to convert their RNA into DNA.

After viral RNA is converted to DNA (now known as a ‘provirus’), it is integrated into the cell’s genome. This is accomplished by the integrase enzyme, which cuts the host cell’s genome and slips in the viral genetic material. Once integrated into the cell’s DNA, the provirus may lie dormant for a long time. However, if the cell is active, the viral genes instruct the cell to produce new viral proteins using the HIV genetic material as a blueprint.

These viral proteins are originally produced in the form of long strands, called polyproteins, that must be cut up into smaller pieces before they can be assembled into new viral components. This is accomplished by the protease enzyme. Next, the newly copied viral genome, proteins, and enzymes are packaged together, enclosed in a new capsid, and ‘bud’ out through the cell membrane to form a complete new virus particle.