Unspliced retroviral RNA is used for both translation of structural proteins and for encapsidation into virions. Although much is now known about how unspliced HIV RNA exists in the nucleus, little is known about the mechanism of trafficking of the RNA between the compartments for translation or encapsidation once the RNA reaches the cytoplasm. This application seeks to test the hypothesis that HIV-1 unspliced RNA forms two functionally distinct pools that are determined by viral sequences: one pool for mRNA translation, and a second pool for encapsidation. The first specific aim of this application is to characterize the metabolism of RNA expressed from simplified HIV-1 genomes that contain distinct elements to facilitate cytoplasmic transport of unspliced RNA (such as Rev, the CTE from MPMV, and an element in the HSV tk gene). The second specific aim is to define the cis and trans-acting domain that modulate trafficking of HIV-1 RNA in the cytoplasm.
