Friday, May 30, 2025
5/30/2025
MAIDS RESISTANCE-ASSOCIATED GENE EXPRESSION IN SECONDARY LYMPHOID ORGANS - DESCRIPTION (provided by applicant): Although the Human Immunodeficiency Virus (HIV) is known to cause an acquired immune deficiency syndrome (AIDS) in humans, the specific mechanisms of immune compromise are poorly understood. Well-characterized model systems that employ inbred animal strains, such as Murine Leukemia Virus (MuLV)-induced murine AIDS (MAIDS), can be used to help define possible immune events that may be salient to resolving the pathways that lead to retroviral persistence and immune deficiency. In our previous work, a DNA microarray approach was used to detect resistance-associated gene expression patterns during the first week of infection. This work generated data suggesting many genes with differential patterns, and two particular families; a set of enzymes that showed much higher expression in the lymph nodes of resistant animals as early as 3 days post infection, and chemotactic signals that significantly differed between the two strains by the end of the first week. These genes and their protein products will be pursued further in the current study, which proposes to quantify these differential responses (both at the level of transcription and translation), expand our understanding of the initial timing of the onset of gene expression and search for the source of these potential susceptibility- or resistance-determining signals. A clearer understanding of these early immune mechanisms will shed light on the general mammalian response to retroviral infection, and could help elucidate pathways relevant to HIV-induced AIDS. PUBLIC HEALTH RELEVANCE: It is still unclear exactly how infection with HIV leads to acquired immune deficiency in humans (AIDS). In order to address these questions, animal models of immune deficiency are often employed, such as the mouse model of AIDS (MAIDS). The current study relies on this mouse model system, and two common inbred strains of mouse, to evaluate how and why one animal strain resists disease after infection with the relevant retrovirus and the other develops symptoms similar to human AIDS. Specifically, genes that are active in the immune organs of the resistant animal shortly after infection will be studied for their potential importance to disease resistance and for their source. Any information gathered from these studies could be relevant to human AIDS and may lead to promising studies to fight this devastating acquired immune deficiency disorder.
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