|Adenovirus vectors block human immunodeficiency virus-1 replication in human alveolar macrophages by inhibition of the long terminal repeat.
|Year of Publication
|Kaner RJ, Santiago F, Rahaghi F, Michaels E, Moore JP, Crystal RG
|Am J Respir Cell Mol Biol
|Adenoviridae, 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.
|Am. J. Respir. Cell Mol. Biol.
|PubMed Central ID
|AI45463 / AI / NIAID NIH HHS / United States
R01 HL59861 / HL / NHLBI NIH HHS / United States
Submitted by alp2017 on January 27, 2015 - 6:46am