Children infected with HIV, in contrast to infected adults, often have higher virus loads and progress to AIDS faster. It is widely accepted that destruction of CD4+ T cells is the primary cause of immunodeficiency in HIV-1 infected adults and children. Macrophages, important cell components of the innate immune system and link between innate and adaptive immunity, are also important targets of HIV/SIV infection. Here, we propose to demonstrate that, in addition to the CD4+ T cells, monocytes/macrophages are also heavily involved in the rapid progression to AIDS in HIV infected children. We have recently shown that the massive turnover of peripheral monocytes associated with death of tissue macrophages correlates with AIDS progression and is a better predictive marker for AIDS progression in adult macaques than CD4+ T cell decline. Our preliminary study also showed that in contrast to adult SIV infected monkeys, a very homogeneous high monocyte turnover was observed in all SIV-infected pediatric monkeys soon after infection. This turnover rate was equivalent to that observed in the adult infected monkeys in the terminal stages of AIDS. Our hypothesis is that massive early damage of tissue macrophages by SIV is the missing link that may explain the mechanism of rapid progression in pediatric AIDS.
Although the use of antiretroviral medications has reduced mother to child transmission (MTCT) of HIV dramatically in developed countries, the number of pediatric HIV-1 infections continues to increase worldwide, especially in developing countries. Therefore, it is still imperative to understand pediatric HIV-1 pathogenesis to design effective prevention strategies and/or a successful pediatric HIV-1 vaccine. Destruction of CD4+ T cells is considered to be the main cause of immunodeficiency resulting from AIDS virus infection in humans as well as in the SIV/macaque animal model of AIDS. Macrophages provide an important link between the innate immune system and l acquired immunity, and furthermore, are also important targets of HIV/SIV infection. Thus, this study focuses on the importance of monocyte/macrophages in the pathogenesis of rapid progression to AIDS in the SIV/macaque model of pediatric AIDS.
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