Human immunodeficiency virus (HIV) infection of host cells initiates innate immune signaling pathways that result in the expression of type I interferons and pro?inflammatory cytokines that interfere with the life cycle of the virus. The virus can bring about measures that not only allow it to escape detection within the cell, but also to use the components of the immune signaling pathways for its own advantage. Studies of mechanisms by which HIV evades the antiviral innate immune responses provide the scientific impetus to characterize the genetic polymorphisms that can affect components of the host signaling pathways. We will conduct a cohort study to determine whether the host proteins identified by genome?wide functional screens for which a plausible biological mechanism of action for the gene is found contributes to HIV/AIDS susceptibility. We will look at the association between genetic variants (both known and previously unknown) and HIV/AIDS susceptibility using biological samples and information obtained from men enrolled in the Multicenter AIDS Cohort Study (MACS). This will allow us to undertake detailed studies of sufficient sample size to distinguish the proposed effect of a factor of functional relevance from no effect convincingly. Our objective is to undertake a
When applied to HIV/AIDS, a systems biology model will predict the response of cellular mechanisms that are used to detect and defend against the virus. The identification of mutations that influence the activity of a protein may help to define new therapies. Thus, the proposed research can positively impact public health by contributing to the understanding and treatment of HIV/AIDS.
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