473 Dynamic Gene Expression Profiling in Lymphatic Tissues Reveals Prominence of Innate Defenses in Controlling HIV-1 Infection In Vivo and Genes Involved in Inflammation, Tissue Damage, and Repair After Treatment Q. Li*1, T. Schacker1, J. Carlis2, G. Beilman1, P. Nguyen1, A. T. Haase1 1Univ of Minnesota Med Sch, Minneapolis and 2Univ of Minnesota Inst of Technology, Minneapolis
Background: The progression of HIV-1 infection in secondary lymphoid organs, the main site of virus production and storage, is slow, in contrast to the rapid turnover of productively infected cells in vivo and dynamics of infection in vitro.
Methods: To identify host factors that slow the progress of infection in vivo, we profiled gene expression by using microarrays in serial lymph node biopsies of HIV-1 infected individuals before and after initiating antiretroviral therapy. We discovered genes mainly in the innate immune system whose expression suppresses viral replication in vivo, and a subset of genes and genes encoding transcriptional regulators that enable continued viral replication. Results: This systemic view of gene expression in HIV-1 infected lymph nodes thus reveals a balance between immune defenses and activation mechanisms that partly control and slow, but do not prevent, HIV-1 propagation in vivo. We also discovered the genes in the gene expression profiles that before initiating antiretroviral therapy moderate the pathological effects of chronic immune activation to slow the rate of tissue injury and the genes expressed after initiating treatment related to the early stages of repopulation and repair of lymphatic tissues.
Conclusions: We will discuss new therapeutic approaches based on this microarray analysis that could tip the balance toward greater constraints on viral replication and increase the effectiveness of current antiretroviral therapy. We will also discuss new therapeutic approaches based on altering the balance between mediators and moderators of chronic immune activation that cause tissue injury.
