This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gao, H.-Q.
Right arrow Articles by Hughes, S. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gao, H.-Q.
Right arrow Articles by Hughes, S. H.

 Previous Article  |  Next Article 

Journal of Virology, December 2001, p. 11874-11880, Vol. 75, No. 23
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.23.11874-11880.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

RNase H Cleavage of the 5' End of the Human Immunodeficiency Virus Type 1 Genome

Hong-Qiang Gao,1,dagger Stefan G. Sarafianos,2 Edward Arnold,2 and Stephen H. Hughes1,3,*

ABL-Basic Research Program1 and HIV Drug Resistance Program,3 National Cancer Institute---Frederick, Frederick, Maryland 21702-1201, and Center for Advanced Biotechnology and Medicine and Chemistry Department, Rutgers University, Piscataway, New Jersey 08854-56382

Received 21 June 2001/Accepted 22 August 2001

The synthesis of retroviral DNA is initiated near the 5' end of the RNA. DNA synthesis is transferred from the 5' end to the 3' end of viral RNA in an RNase H-dependent step. In the case of human immunodeficiency virus type 1 (HIV-1) (and certain other retroviruses that have complex secondary structures at the ends of the viral RNA), there is the possibility that DNA synthesis can lead to a self-priming event that would block viral replication. The extent of RNase H cleavage must be sufficient to allow the strand transfer reaction to occur, but not so extensive that self-priming occurs. We have used a series of model RNA substrates, with and without a 5' cap, to investigate the rules governing RNase H cleavage at the 5' end of the HIV-1 genome. These in vitro RNase H cleavage reactions produce an RNA fragment of the size needed to block self-priming but still allow strand transfer. The cleavages seen in vitro can be understood in light of the structure of HIV-1 reverse transcriptase in a complex with an RNA/DNA substrate.

* Corresponding author. Mailing address: HIV Drug Resistance Program, National Cancer Institute-FCRDC, P.O. Box B, Building 539, Room 130A, Frederick, MD 21702-1201 Phone: (301) 846-1619. Fax: (301) 846-6966. E-mail: hughes{at}ncifcrf.gov.

dagger Present address: E-Centive, Bethesda, MD 20817.

Journal of Virology, December 2001, p. 11874-11880, Vol. 75, No. 23
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.23.11874-11880.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Schultz, S. J., Zhang, M., Champoux, J. J. (2006). Sequence, Distance, and Accessibility Are Determinants of 5'-End-directed Cleavages by Retroviral RNases H. J. Biol. Chem. 281: 1943-1955 [Abstract] [Full Text]  
  • Wisniewski, M., Chen, Y., Balakrishnan, M., Palaniappan, C., Roques, B. P., Fay, P. J., Bambara, R. A. (2002). Substrate Requirements for Secondary Cleavage by HIV-1 Reverse Transcriptase RNase H. J. Biol. Chem. 277: 28400-28410 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»