Skip NavigationSkip to Content

Targeting the HIV entry, assembly and release pathways for anti-HIV gene therapy

  1. Author:
    Joshi, A.
    Garg, H.
    Ablan, S.
    Freed, E. O.
    Nagashima, K.
    Manjunath, N.
    Shankar, P.
  2. Author Address

    [Joshi, A; Garg, H; Manjunath, N; Shankar, P] Texas Tech Univ, Hlth Sci Ctr, Dept Biomed Sci, Ctr Excellence Infect Dis, El Paso, TX 79905 USA [Joshi, A; Garg, H] Texas Tech Univ, Hlth Sci Ctr, Dept Pediat, El Paso, TX 79905 USA [Ablan, S; Freed, EO] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA [Nagashima, K] NCI, Electron Microscope Lab, Res Technol Program, SAIC Frederick, Frederick, MD 21702 USA;Joshi, A (reprint author), Texas Tech Univ, Hlth Sci Ctr, Dept Biomed Sci, Ctr Excellence Infect Dis, El Paso, TX 79905 USA;anjali.joshi@ttuhsc.edu premlata.shankar@ttuhsc.edu
    1. Year: 2011
    2. Date: Jul
  1. Journal: Virology
    1. 415
    2. 2
    3. Pages: 95-106
  2. Type of Article: Article
  3. ISSN: 0042-6822
  1. Abstract:

    Targeting the HIV entry and assembly pathways holds promise for development of novel anti-HIV gene therapy vectors. We characterized discrete dominant negative (DN) Gag and Envelope mutants for their anti-HIV-1 activity. We show here that capsid mutants (Q155N and Y164A) are more potent inhibitors of WT HIV than the matrix mutant 1GA. Both the Envelope mutants tested, V513E and R515A, were equally effective and a combination of Gag and Envelope DN genes significantly enhanced potency. Interestingly, the DN mutants acted at multiple steps in the virus life cycle rather than solely disrupting virus release or infection. Inhibition mediated by R515A could be partially attributed to the Envelope cytoplasmic tail, as deletion of R515A tail partially abrogated its DN effect. Finally, the Y164A/R515A double mutant expressed in a lentiviral vector was effective at inhibiting HIV replication in CD34+ hematopoietic stem cell-derived macrophages, demonstrating the therapeutic potential of our approach. Published by Elsevier Inc.

    See More

External Sources

  1. DOI: 10.1016/j.virol.2011.03.028
  2. WOS: 000291713500003

Library Notes

  1. Fiscal Year: FY2010-2011
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel