Life Cycle of a Virus

HIV stands for Human Immunodeficiency Virus. Viruses are tiny packages of genetic material that use cells of other organisms, called "host cells," to reproduce. Each type of virus can use only very specific types of cells as its host.

In a typical viral life cycle, the virus binds to a host cell and inserts its genetic material into the cell. In so doing, the virus mobilizes the resources of the host cell to produce and release hundreds to thousands more viruses. Often, this process destroys the host cell's ability to function and/or causes it to die. The new virus particles disperse to find more host cells to repeat the process. Of course, many virus particles are destroyed one way or another before they locate an appropriate host cell.

The Host Cells of HIV

HIV binds to specific substances found on the surface of some human cells. (25) (The family of coreceptors which has received considerable press are some of these proteins. It has been found that a small percentage of people lack one of these cofactors necessary for HIV to bind to their cells. These fortunate people, therefore, are extremely resistant to HIV. While interesting, this is not likely to lead to a viable therapy. (There is no in vivo precedent for total double deletion gene therapy.)) The cells with these substances become the host cells for HIV. These are the nerves, sperm, gut, and two types of immune system or white blood cells - macrophages and T₄ cells (also called helper T cells or CD4 cells). Not all these cell types contain the same amount of the requisite substances, so some are more likely to be infected by HIV than others, especially macrophages and T₄ cells.

(Note: It is largely because HIV infects nerve cells that many researchers believe HIV is impossible to completely eradicate once an infection is established. For more information see Note on "Cures".)

HIV to AIDS - The Direct Infection Model

T₄ cells regulate the immune system. According to the direct infection model, a person's immune system collapses because HIV infects and kills so many T₄ cells that there are no longer enough to do their job. Specifically, this model claims that loss of immune function is caused solely by the death of infected T₄ cells. The direct infection model proposes the following progression:

When a person is first exposed to HIV, the virus infects a few cells, reproduces, and rapidly spreads via the bloodstream and lymph nodes. However, the person's healthy immune system rapidly controls the infection. But since the immune system cannot completely eliminate the virus, HIV lingers, slowly infecting more and more cells, especially T₄ cells. T₄ cells control the entire immune system, so as they are killed the immune system weakens. Eventually the virus infects so many T₄ cells that the immune system collapses, and the body falls victim to various opportunistic diseases that rarely are troublesome in healthy people.

Experimental Evidence Concerning the Direct Infection Model

The direct infection model has guided the research efforts of most scientists. However, those same research efforts have produced many repeated experiments demonstrating the implausibility of this model. These experiments have led an increasing number of AIDS experts to acknowledge that the direct infection model is problematic. Here are some of the findings from these experiments:

1% Infection Rate: Less than 1% of T₄ cells are actually found to be infected with HIV, even in people with full-blown AIDS. Nonetheless, 80% or greater of those same cells are destroyed. Although it is possible, such dramatic loss of function is unlikely from such a small infection rate. (66)

Failure of Uninfected Cells: According to the direct infection model, T₄ cells fail to function only because they are infected. Therefore, all uninfected cells should be healthy. However, research has found large numbers of T₄ cells which cannot function normally (reduced functionality and/or anergy), yet are not infected with HIV. (20, 73-76)

Wrong Cells Dying: Furthermore, infected T₄ cells are not dying, and the dying cells are not infected. In one study of T₄ cells from a person with AIDS, 1031 cells were uninfected but dying (apoptosis), 696 were infected but not dying, and none were infected and dying. This is the exact opposite of what is predicted by the direct infection model, which asserts that cells are dying because they are infected. (77, 78)

Immune Failure Before T₄ cell Death: In order for T₄ cell death by direct infection to be the cause of immune failure, T₄ cell death needs to occur before the immune system fails. However, the literature continually shows broad immunologic defects appearing prior to T₄ cell loss. (22)

Normal Immune Function During Initial Infection: The number of HIV particles in the blood and the fraction of infected T₄ cells are highest during initial infection, rather than during full-blown AIDS (70). Nonetheless, the immune system is able to function well during initial infection. If immune system collapse were caused solely by the death of T₄ cells because of direct HIV infection, then the immune system should collapse, or at least suffer, during initial infection.

Failure of Uninfected T₄ Cells to Mature: When people with full-blown AIDS are given anti-viral drugs their viral levels can be reduced to below detectible levels. During these treatments, HIV is not reproducing and infecting new cells, and the T₄ cell count returns to seemingly normal levels. However, the new T₄ cells are clones of existing T₄ cells, and are therefore responsive only to old pathogens. Naive (new, unconditioned) T₄ cells being produced by the bone marrow do not mature properly even though the viral level is so low. Consequently, the immune system does not regain its ability to respond to new pathogens. The direct infection model has no way to explain the failure of naive T₄ cells to mature or the failure of the body to reconstitute the immune system in the near absence of HIV.

Decline of T₈ Cells: Finally, T₈ cells (also called cytotoxic T cells, killer T cells, or CD8 cells) cannot be infected by HIV, but nonetheless decline in numbers during AIDS. This fact is also unexplained by the direct infection model. (10, 11, 15, 16)

Conclusion

These findings are devastating to the credibility of the direct infection model as a sole explanation of how HIV causes the immune system to collapse. It is worth noting that the evidence does indicate that some portion of the damage to the immune system in AIDS is caused by the direct infection of T₄ cells by HIV. However, the direct infection model asserts that this is the only cause of the failure of T₄ cells. It is this assertion that does not appear to be supported by the research. As a result, more and more researchers are seeking a new model which will be more predictive and explain more of the available evidence. For an explanation of one such model please see Autoimmune Model, the next section.

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