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Journal of Virology, July 2003, p. 7623-7634, Vol. 77, No. 13
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.13.7623-7634.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Type 2 Reverse Transcriptase Activity in Model Systems That Mimic Steps in Reverse Transcription

Klara Post,1 Jianhui Guo,1 Kathryn J. Howard,2 Michael D. Powell,3 Jennifer T. Miller,4 Amnon Hizi,5 Stuart F. J. Le Grice,4 and Judith G. Levin1*

Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, Bethesda, Maryland 20892,1 Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106,2 Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, Georgia 30310,3 HIV Drug Resistance Program, National Cancer Institute at Frederick, Frederick, Maryland 21702,4 Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel5

Received 4 September 2002/ Accepted 4 April 2003

Human immunodeficiency virus type 2 (HIV-2) infection is a serious problem in West Africa and Asia. However, there have been relatively few studies of HIV-2 reverse transcriptase (RT), a potential target for antiviral therapy. Detailed knowledge of HIV-2 RT activities is critical for development of specific high-throughput screening assays of potential inhibitors. Here, we have conducted a systematic evaluation of HIV-2 RT function, using assays that model specific steps in reverse transcription. Parallel studies were performed with HIV-1 RT. In general, under standard assay conditions, the polymerase and RNase H activities of the two enzymes were comparable. However, when the RT concentration was significantly reduced, HIV-2 RT was less active than the HIV-1 enzyme. HIV-2 RT was also impaired in its ability to catalyze secondary RNase H cleavage in assays that mimic tRNA primer removal during plus-strand transfer and degradation of genomic RNA fragments during minus-strand DNA synthesis. In addition, initiation of plus-strand DNA synthesis was much less efficient with HIV-2 RT than with HIV-1 RT. This may reflect architectural differences in the primer grip regions in the p66 (HIV-1) and p68 (HIV-2) palm subdomains of the two enzymes. The implications of our findings for antiviral therapy are discussed.

* Corresponding author. Mailing address: Laboratory of Molecular Genetics, NICHD, Building 6B, Room 216, NIH, Bethesda, MD 20892-2780. Phone: (301) 496-1970. Fax: (301) 496-0243. E-mail: jlevin{at}mail.nih.gov.

Journal of Virology, July 2003, p. 7623-7634, Vol. 77, No. 13
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.13.7623-7634.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Post, K., Kankia, B., Gopalakrishnan, S., Yang, V., Cramer, E., Saladores, P., Gorelick, R. J., Guo, J., Musier-Forsyth, K., Levin, J. G. (2009). Fidelity of plus-strand priming requires the nucleic acid chaperone activity of HIV-1 nucleocapsid protein. Nucleic Acids Res 37: 1755-1766 [Abstract] [Full Text]  
  • Held, D. M., Kissel, J. D., Thacker, S. J., Michalowski, D., Saran, D., Ji, J., Hardy, R. W., Rossi, J. J., Burke, D. H. (2007). Cross-Clade Inhibition of Recombinant Human Immunodeficiency Virus Type 1 (HIV-1), HIV-2, and Simian Immunodeficiency Virus SIVcpz Reverse Transcriptases by RNA Pseudoknot Aptamers. J. Virol. 81: 5375-5384 [Abstract] [Full Text]  
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