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How HIV Causes Disease


I set out to discover whether all the germinal centers in HIV-infected lymph nodes are so heavily infected. I used my special in situ hybridization technique, a technique that reminds me of the story of Cinderella. You remember that the crystal slipper would fit only Cinderella's foot and none other. Likewise, my "probes" were specific for the HIV in infected tissues and would identify only that virus. I made the probes especially sensitive with radioisotopes and by complicated genetic engineering. With the help of Drs. Phillip Pizzo, Ellen Chadwick, and others, I was able to obtain 12 other lymph nodes from both adults and children. All of them had lots of virus in the germinal centers.

In Germany, my colleagues had been studying lymph nodes from people with HIV infection since the beginning of the epidemic. After a few weeks of intense work we had the answer. Everyone with HIV disease had the virus in the germinal centers of their lymph nodes.

Then, almost by accident, we performed a crucial experiment. We cut a lymph node and put several slices of the tissue onto microscope slides. We then digested one of the tissues with an enzyme that breaks down proteins, while an identical slice of tissue was left untreated with an enzyme. The results of this experiment are shown in Figures 3a and 3b. The tissue treated with the enzyme that digests proteins shows a strong HIV signal, while the untreated tissue is negative. How would you interpret this finding?

Figure 3a

Figure 3b

Figures 3a, 3b The same germinal centers from two consecutive lymph node tissue sections seen with the darkfield microscope. The tissue in Figure 3a was not digested with a protease to remove proteins. The tissue in Figure 3b was digested with protease before in situ hybridization. HIV in the germinal center is shown as white (silver grains reflect light).

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