Adenovirus vectors block human immunodeficiency virus-1 replication in human alveolar macrophages by inhibition of the long terminal repeat

Robert J. Kaner, Francisco Santiago, Franck Rahaghi, Elizabeth Michaels, John P. Moore, Ronald G. Crystal

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3 Citations (Scopus)

Abstract

Heterologous viruses may transactivate or suppress human immunodeficiency virus (HIV)-1 replication. An adenovirus type 5 gene transfer vector (Ad5) HIV-1 vaccine was recently evaluated in a clinical trial, without efficacy. In this context, it is relevant to ask what effect Ad vectors have on HIV-1 replication, particularly in cells that are part of the innate immune system. Infection of HIV-1-infected human alveolar macrophages (AMs) obtained from HIV-1+ individuals with an Ad vector containing no transgene (AdNull) resulted in dose-responsive inhibition of endogenous HIV-1 replication. HIV-1 replication in normal AMs infected with HIV-1 in vitro was inhibited by AdNull with a similar dose response. Ad reduced AM HIV-1 replication up to 14 days after HIV-1 infection. Fully HIV-1-infected AMs were treated with 3′-azido-3′- deoxythymidine, after which Ad infection still inhibited HIV-1 replication, suggesting a postentry step was affected. Substantial HIV-1 DNA was still produced after Ad infection, as quantified by TaqMan real-time PCR, suggesting that the replication block occurred after reverse transcription. AdNull blocked HIV-1 long terminal repeat (LTR) transcription, as assessed by an vesicular stomatitis virus G protein pseudotyped HIV-1 LTR luciferase construct. The formation of HIV-1 DNA integrated into the host chromosome was not inhibited by Ad, as quantified by a two-step TaqMan real-time PCR assay, implying a postintegration block to HIV-1 replication. These data indicate that Advectors are inhibitory to HIV-1 replication in human AMs based, in part, on their ability to inhibit LTR-driven transcription.

Original languageEnglish
Pages (from-to)234-242
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume43
Issue number2
DOIs
Publication statusPublished - 1 Aug 2010

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Keywords

  • Adenovirus
  • HIV-1 replication
  • Human alveolar macrophage

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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