The objective of this work is to provide a more detailed description of the role of the human immunodeficiency virus (HIV) reverse transcriptase (RT) during generation of proviral DNA, than is currently available. specifically, we will explore in greater detail a unique double stranded RNA dependent ribonuclease activity of HIV-1 RT which we have recently identified. This RNase activity appears to be an integral part of the RT protein, yet it may be distinct of the well characterized DNA polymerase and RNaseH activities. We will characterize this unique enzymatic activity by biochemical and genetic methods. The role of RNase activity in proviral DNA synthesis will be analyzed in vitro and during virus infection of tissue culture cells. In light of the public health danger posed by HIV, the clearer understanding of proviral DNA synthesis which this work will provide, is essential. Furthermore, studies of the unique RNaseD activity of RT may lead to a new interventional point in the HIV life cycle and to the development of a new class of inhibitors of HIV replication.
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