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How HIV Causes Disease

Here is how we interpreted it: The tissue with a positive HIV reaction must have contained virus coated (cloaked) with proteins that were uncloaked by removing those proteins. The untreated tissue must have the HIV's RNA tightly covered with proteins, such as antibodies, which prevented the probes from attaching to the viral RNA. Using an electron microscope, my colleagues had already shown that virus particles in the germinal centers attached to the surface of specialized cells called follicular dendritic cells, or FDCs. Later we were able to estimate that there may be as many as 1 X108 virus particles per cubic centimeter of germinal center. The germinal centers are not very well understood. Why germinal centers would store antibody-covered virus particles such as HIV is especially problematic. However, it has been known for 25 years that germinal centers do contain deposits of foreign proteins combined with antibodies, and that CD4+ T cells (the targets of HIV) migrate through the germinal centers. We believe that HIV is coated with antibodies in the blood, and then the virus is stored in the germinal centers.

These results were confirmed by Dr. Anthony Fauci and his colleagues at the National Institutes of Health using polymerase chain reaction (PCR) technology. In October of 1995, at the University of Virginia Medical Center, Dr. Gregory Burton and his co-workers reported a beautiful set of experiments that provided the last piece to the puzzle. They showed that the virus, although covered with antibodies and attached to the follicular dendritic cells, is still infectious. These findings explain why the virus takes years to decades to cause disease. As susceptible T cells migrate through the germinal centers (and T cells do this constantly), a few cells are infected at each passage. These infected T cells return to the circulation and produce more virus, which in turn combines with antibody and returns to the lymph node. This process is repeated day after day until the numbers of T cells becoming infected compromise the immune system. While the amounts of virus in the circulating blood may go up or down in response to antiviral agents, the virus in the germinal centers is protected from drugs or antibodies, and as long as it remains in the tissues it can infect new cells­­even though the process is very inefficient. Now this explanation may seem very complicated. Here is a diagram of how it works:

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