Lymphatic tissues are the major site of HIV-1 replication, persistence and pathology prior to anti-retroviral treatment. After treatment suppresses viral replication, the pathological changes can be reversed to a variable extent. With the objective of identifying molecular bases for the pathological and reparative processes in HIV-1 infected lymphatic tissues, a preliminary microarray study was undertaken of gene expression in lymph node biopsies from HIV-1 infected patients before and after treatment. The study revealed a set of treatment-responsive genes related to host defenses, inflammatory pathology, and tissue repair. The overall objective of the proposed studies is to extend the gene profiling studies to gain further insight into the pathogenesis of HIV-1 infection in lymphatic tissues and the response to treatment that will translate into optimal timing and effectiveness of treatment. To this end, in specific aim 1 larger numbers of patients at different stages of HIV-1 infection will undergo lymph node biopsies for microarray analysis prior to and after antiretroviral treatment.
In specific aim 2, in situ hybridization, immunohistochemical staining and quantitative image analysis will be used to link changes in gene expression to cells and anatomic sites and structures. Collectively, insights into pathological and reparative processes could lead to new approaches to decreasing the pathological consequences of infection and to new therapeutic strategies to enhance immune reconstitution.
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