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The capsid-spacer peptide 1 Gag processing intermediate is a dominant-negative inhibitor of HIV-1 maturation

  1. Author:
    Checkley, M. A.
    Luttge, B. G.
    Soheilian, F.
    Nagashima, K.
    Freed, E. O.

  2. Author Address

    [Checkley, Mary Ann; Luttge, Benjamin G.; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Soheilian, Ferri; Nagashima, Kunio] NCI, Image Anal Lab, Res Technol Program, SAIC Frederick, Frederick, MD 21702 USA.;Freed, EO, NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Bldg 535,Rm 108,1050 Boyles St, Frederick, MD 21702 USA.;efreed@nih.gov
    1. Year: 2010
    2. Date: Apr
  2. Journal: Virology
    1. 400
    2. 1
    3. Pages: 137-144
  4. Type of Article: Article
  5. ISSN: 0042-6822
  1. Abstract:

    The human immunodeficiency virus type 1 (HIV-1) maturation inhibitor bevirimat disrupts virus replication by inhibiting the cleavage of the capsid-spacer peptide 1 (CA-SP1) Gag processing intermediate to mature CA. The observation that bevirimat delays but does not completely block CA-SP1 processing suggests that the presence of uncleaved CA-SP1 may disrupt the maturation process in trans. In this study, we validate this hypothesis by using a genetic approach to demonstrate that a non-cleavable CA-SP1 Mutant exerts a dominant-negative effect on Maturation of wild-type HIV-1. In contrast, a mutant in which cleavage can occur internally within SP1 is significantly less potent as a dominant-negative inhibitor. We also show that bevirimat blocks processing at both the major CA-SP1 cleavage site and the internal site. These data underscore the importance of full CA-SP1 processing for HIV-1 maturation and highlight the therapeutic potential of inhibitors that target this Gag cleavage event. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.virol.2010.01.028
  3. View record in Web of Science®
  4. WOS: 000275764900014

Library Notes

  1. Fiscal Year: FY2009-2010
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