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Human immunodeficiency virus type 1 nucleocapsid zinc-finger mutations cause defects in reverse transcription and integration

  1. Author:
    Thomas, J. A.
    Gagliardi, T. D.
    Alvord, W. G.
    Lubomirski, M.
    Bosche, W. J.
    Gorelick, R. J.
  2. Author Address

    NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Basic Res Program,AIDS Vaccine Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Comp & Stat Serv, Stat Consulting Serv, Frederick, MD 21702 USA.;Gorelick, RJ, NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Basic Res Program,AIDS Vaccine Program, POB B,Bldg 535,Room 410, Frederick, MD 21702 USA.;jathomas@ncifcrf.gov gagliardi@ncifcrf.gov gwa@css.ncifcrf.gov mlubomir@prdus.jnj.com bosche@ncifcrf.gov gorelick@ncifcrf.gov
    1. Year: 2006
    2. Date: Sep
  1. Journal: Virology
    1. 353
    2. 1
    3. Pages: 41-51
  2. Type of Article: Article
  3. ISSN: 0042-6822
  1. Abstract:

    The nucleocapsid (NC) protein from HIV-1 contains two zinc-fingers, both of which are necessary for virus replication. This is the first in-depth study that presents the effects of nucleocapsid zinc-finger substitutions on the kinetics of reverse transcription and integration. Over a 72-h time-course of infection, the quantities of viral DNA (vDNA) observed with viruses containing either the nucleocapsid His23Cys or His44Cys mutations were significantly lower than those observed in infections with virus containing wild-type NC. In addition, the kinetics of vDNA formation and loss were significantly different from wild-type. The kinetic profiles observed indicated reduced vDNA stability, as well as defects in reverse transcription and integration. Overall, the defect in integration was much more pronounced than the reverse transcription defects. This suggests that the principal reason for the replication defectiveness of these mutant viruses is impairment of integration, and thus demonstrates the critical importance of NC in HIV-1 infection. (c) 2006 Elsevier Inc. All rights reserved.

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External Sources

  1. DOI: 10.1016/j.virol.2006.05.014
  2. WOS: 000240512100006

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