The Infectiveness and Pathogenicity of HIV

There is a strong association between HIV infection and the immune system. HIV is often spread by dendritic cells, whichpick up the virus and carry it to the lymphoid organs. Thereit contacts cells of the immune system, most notably activatedT cells, and stimulates an initial strong immune response.

To be infective, HIV must go through the steps of attachment,fusion, and entry (Figure 2). Attachment to the target cell depends on the glycoprotein spike (gp120) combining with the CD4 ⁺ receptor. Approximately 65,000 of these receptors are found on each CD4 ⁺ T helper cell, which is the main target of HIV infection. Certain coreceptors are also required. Macrophages and monocytes also carry CD4 molecules. (Many cells that do not express the CD4 molecule can also become infected, an indication that other receptors can also serve for infection by HIV).

In the host cell, viral RNA is released and transcribed into DNA by the enzyme reverse transcriptase. This viral DNA then becomes integrated into the chromosomal DNA of the host cell. The DNA may control the production of an active infection in which new viruses bud from the host cell (Figure 3b).

Figure 3 Latent and active HIV infection in CD4+ T cells.

Alternatively, this integrated DNA may not produce new HIV but remains hidden in the host cell's chromosome as a provirus (Figure 3a and Figure 4a). HIV produced by a host cell is not necessarily released from the cell but may remain as latem virions in vacuoles within the cell (Figure 4b). In fact, a subset of the HIV-infected cells, instead of being killed, become long-lived memory T cells in which the reservoir of latent HIV can persist for decades. This ability of the virus to remain as a

provirus or latent virus within host cells shelters it from the immune system. Another way HIV evades the immune system is cell-cell fusion, by which the virus moves from an infected cell to an adjacent uninfected cell.

The virus also evades immune defenses by undergoing rapid antigenic changes. Retroviruses, with the reverse transcriptase enzyme step, have a high mutation rate compared to DNA viruses. They also lack the corrective "proofreading" capacity of DNA viruses. As a result, a mutation is probably introduced at every position in the HIV genome many times each day in an infected person. This may amount to an accumulation of 1 million variants of the virus in an asymptomatic person and 100 million variants during the final stages of the infection. These dramatic numbers illustrate the potential problems of drug resistance and obstacles to the development of vaccines and diagnostic tests.

Дата добавления: 2014-01-11