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

TitleAdenovirus vectors block human immunodeficiency virus-1 replication in human alveolar macrophages by inhibition of the long terminal repeat.
Publication TypeJournal Article
Year of Publication2010
AuthorsKaner RJ, Santiago F, Rahaghi F, Michaels E, Moore JP, Crystal RG
JournalAm J Respir Cell Mol Biol
Date Published2010 Aug
KeywordsAdenoviridae, Bronchoalveolar Lavage, Bronchoscopy, Gene Transfer Techniques, Genetic Vectors, HIV Long Terminal Repeat, HIV-1, Humans, Macrophages, Alveolar, Reverse Transcriptase Polymerase Chain Reaction, Time Factors, Transcription, Genetic, Transgenes, Virus Replication

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 Ad vectors are inhibitory to HIV-1 replication in human AMs based, in part, on their ability to inhibit LTR-driven transcription.

Alternate JournalAm. J. Respir. Cell Mol. Biol.
PubMed ID19805482
PubMed Central IDPMC2937233
Grant ListAI45463 / AI / NIAID NIH HHS / United States
R01 HL59861 / HL / NHLBI NIH HHS / United States

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