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Antiviral Agents

Saquinavir Inhibits Early Events Associated with Establishment of HIV-1 Infection: Potential Role for Protease Inhibitors in Prevention

Martha Stefanidou, Carolina Herrera, Naomi Armanasco, Robin J. Shattock
Martha Stefanidou
Centre for Infection, Department of Cellular and Molecular Medicine, St. George's University of London, London, United Kingdom
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Carolina Herrera
Centre for Infection, Department of Cellular and Molecular Medicine, St. George's University of London, London, United Kingdom
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Naomi Armanasco
Centre for Infection, Department of Cellular and Molecular Medicine, St. George's University of London, London, United Kingdom
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Robin J. Shattock
Centre for Infection, Department of Cellular and Molecular Medicine, St. George's University of London, London, United Kingdom
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DOI: 10.1128/AAC.00399-12
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ABSTRACT

The maturation of newly formed human immunodeficiency virus type 1 (HIV-1) virions is a critical step for the establishment of productive infection. We investigated the potential of saquinavir (SQV), a protease inhibitor (PI) used in highly active antiretroviral therapy (HAART), as a candidate microbicide. SQV inhibited replication of clade B and clade C isolates in a dose-dependent manner in all cellular models tested: PM-1 CD4 T cells, peripheral blood mononuclear cells (PBMCs), monocyte-derived macrophages (MDMs), and immature monocyte-derived dendritic cells (iMDDCs). SQV also inhibited production of infectious virus in cervical, penile, and colorectal explants cocultured with T cells. Moreover, SQV demonstrated inhibitory potency against trans infection of T cells by in vitro-derived dendritic cells and by primary dendritic cells that emigrate from penile and cervical tissue explants. No cellular or tissue toxicity was detected in the presence of SQV, suggesting that this drug could be considered for development as a component of an effective microbicide, capable of blocking viral maturation and transmission of HIV-1 at mucosal surfaces.

FOOTNOTES

    • Received 20 February 2012.
    • Returned for modification 2 April 2012.
    • Accepted 31 May 2012.
    • Accepted manuscript posted online 4 June 2012.
  • Supplemental material for this article may be found at http://dx.doi.org/10.1128/AAC.00399-12.

  • Copyright © 2012, American Society for Microbiology. All Rights Reserved.
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Saquinavir Inhibits Early Events Associated with Establishment of HIV-1 Infection: Potential Role for Protease Inhibitors in Prevention
Martha Stefanidou, Carolina Herrera, Naomi Armanasco, Robin J. Shattock
Antimicrobial Agents and Chemotherapy Jul 2012, 56 (8) 4381-4390; DOI: 10.1128/AAC.00399-12

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Saquinavir Inhibits Early Events Associated with Establishment of HIV-1 Infection: Potential Role for Protease Inhibitors in Prevention
Martha Stefanidou, Carolina Herrera, Naomi Armanasco, Robin J. Shattock
Antimicrobial Agents and Chemotherapy Jul 2012, 56 (8) 4381-4390; DOI: 10.1128/AAC.00399-12
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