• Virologic and Immunologic Concepts on HIV Transmission (Abstract PL10)
  Speaker: A. Haase
  Authored by Haase, A.; Department of Microbiology, University of Minnesota

Dr. Haase has the unusual ability of making things look simple when, in fact, they are incredibly complex. I have heard him talk a few times and his clarity is amazing. He had a difficult task to tackle during the first plenary Wednesday morning: he explained to us the first "steps" of HIV after infection. He works with a group at the University of Minnesota and they have multiple partnerships beyond the university. He uses a rhesus model of vaginal transmission of SIV to try to answer this question. The findings in the model are confirmed with biopsies of patients during acute infection. In this model rhesus macaques are infected vaginally and then sacrificed 1, 3, 7 and 12 days after the infection. Using in-situ hybridization and immunostaining they are able to identify where the SIV is at each moment and what kind of cells the SIV is infecting.

Initially the virus infects the mucosa. By day 12 there is widespread dissemination. The virus infects not only activated T cells but also resting T cells (against the prevailing "dogma"). In fact, numerically, the infection of resting T cells is even higher than the one of activated T cells at the beginning. The reason for this, according to Haase, is that they are "just there" (in normal mucosa, there are not usually very many activated T cells) and those are the cells that the virus infects initially. As infection progresses and more cells get activated, the virus is more likely to infect them. The virus infects those early resting T cells and basically establishes a long-term reservoir that is impossible to eradicate with currently available antiretroviral therapy.

The virus in the resting T cells is quite inactive and the resting T cells do not express their surface viral antigens. This makes the resting T cells an extremely poor target for elimination by the CTLs, and, because the virus is not really replicating in them, they are also a poor target for antiretroviral therapy. Activated T cells are an easier target for CTLs and also their virus -- which is replicating actively when inhibited by antiretroviral therapy.

The bottom line is that because the virus establishes a long-term reservoir very early during infection, the window of opportunity for making an effective vaccine is narrow. This is the challenge we are facing in the development of an effective preventive vaccine.

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