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J Biol Chem, Vol. 273, Issue 7, 3808-3816, February 13, 1998

Control of Initiation of Viral Plus Strand DNA Synthesis by HIV Reverse Transcriptase

Chockalingam PalaniappanDagger , Jin K. KimDagger , Michele WisniewskiDagger , Philip J. FayDagger §, and Robert A. BambaraDagger

From the Departments of Dagger  Biochemistry & Biophysics and § Medicine and the  Cancer Center, University of Rochester, Rochester, New York 14642

Human immunodeficiency virus reverse transcribes its single-stranded RNA genome making a DNA copy. As synthesis proceeds, the RNA is simultaneously degraded to oligomers; one of these, the polypurine tract, primes synthesis of a plus strand DNA. The viral reverse transcriptase (RT) degrades all of the non-polypurine tract oligomers. We show that unlike other DNA polymerases the retroviral RT can bind either end of an annealed RNA primer, the 5'-end for degradation and the 3'-end for synthesis. The competition between the two binding modes at any primer determines whether it will be extended or degraded. The 5'-end binding can be suppressed in at least two ways. The sequence of the primer can be such that a region at the 5'-end is unannealed or a DNA primer can be annealed just adjacent to the 5'-end of the RNA primer. This promotes binding of RT to the RNA 3'-end, allowing a primer that would normally be degraded to be extended. Implications for human immunodeficiency virus replication and antiviral therapy are discussed.

Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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