THOMAS JEFFERSON UNIVERSITY
Grant: $386,250 - National Institutes of Health - May. 21, 2009
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Award Description: Accumulating evidence has indicated that human immunodeficiency virus type 1 (HIV-1) replication is regulated by cell- or virus-derived miRNAs. Recently, we have found that several cellular miRNAs are involved in establishing and maintaining HIV-1 latency in resting primary CD4 T-lymphocytes. The 3’-termini of various HIV-1 mRNAs are the binding site of a cluster of cellular miRNAs including mir-28, mir-125b, mir-150, mir-223, and mir-382, which is enriched in the resting CD4+ T cells rather than in activated CD4+ cells. The antisense inhibitors of these miRNAs can significantly counteract the inhibitory effects of their corresponding miRNAs upon either HIV-1 protein translation in the resting CD4 T-cells transfected with HIV-1 infectious clone, or HIV-1 production from the resting CD4+ T-cells isolated from HIV-1-infected individuals receiving suppressive highly active antiretroviral treatment (HAART). Besides, we have also found that virion associated cellular miRNA could play a role in HIV-1 replication. As the evidence that miRNAs affect HIV-1 replication is solid, we would like to propose the following projects to systematically examine the effect of cellular miRNAs on HIV-1 replication: (1). Mechanistic studies to further clarify how cellular miRNAs contribute to HIV-1 postintegration latency in resting CD4 T-lymphocytes (2). Further investigate the interaction between cellular miRNAs and the inefficient expression of Tat or Rev and their possible synergetic contribution to HIV-1 latency in resting CD4 T-lymphocytes. Experiments in this proposal are designed to provide a detail understanding of the mechanism how cellular miRNAs affect HIV-1 replication. Such information is crucial for further exploiting the relevance of miRNA manipulation in controlling HIV-1 replication and transmission. Following revised aims are proposed for the two 2-year ARRA award, which will be followed by a two2- year NIAID award.
Project Description: As described in Award Description.
Jobs Summary: Prime Recipient Created - 2 Research Tech B; Retained - 1 Professor (Total jobs reported: 3)
Project Status: Less Than 50% Completed
This award's data was last updated on May. 21, 2009. Help expand these official descriptions using the wiki below.
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