Replication Cycle of HIV

Replication Cycle of HIV

Infection typically begins when an HIV particle, which contains two copies of the HIV RNA, encounters a cell with a surface molecule called cluster designation 4 (CD4). Cells carrying this molecule are known as CD4+ cells.

One or more of the virus's gp120 molecules binds tightly to CD4 molecule(s) on the cell's surface. The binding of gp120 to CD4 results in a conformational change in the gp120 molecule allowing it to bind to a second molecule on the cell surface known as a co-receptor. The envelope of the virus and the cell membrane then fuse, leading to entry of the virus into the cell. The gp41 of the envelope is critical to the fusion process. Drugs that block either the binding or the fusion process are being developed and tested in clinical trials. The Food and Drug Administration (FDA) has approved one of the so-called fusion inhibitors, T20, for use in HIV-infected people.

Studies have identified multiple coreceptors for different types of HIV strains. These coreceptors are promising targets for new anti-HIV drugs, some of which are now being tested in preclinical and clinical studies. Agents that block the co-receptors are showing particular promise as potential microbicides that could be used in gels or creams to prevent HIV transmission. In the early stage of HIV disease, most people harbor viruses that use, in addition to CD4, a receptor called CCR5 to enter their target cells. With disease progression, the spectrum of co-receptor usage expands in approximately 50 percent of patients to include other receptors, notably a molecule called CXCR4. Virus that uses CCR5 is called R5 HIV and virus that uses CXCR4 is called X4 HIV.

Although CD4+ T cells appear to be the main targets of HIV, other immune system cells with and without CD4 molecules on their surfaces are infected as well. Among these are long-lived cells called monocytes and macrophages, which apparently can harbor large quantities of the virus without being killed, thus acting as reservoirs of HIV. CD4+ T cells also serve as important reservoirs of HIV; a small proportion of these cells harbor HIV in a stable, inactive form. Normal immune processes may activate these cells, resulting in the production of new HIV virions.

Cell-to-cell spread of HIV also can occur through the CD4-mediated fusion of an infected cell with an uninfected cell.