Adenovirus Vectors Block Human Immunodeficiency Virus–1 Replication in Human Alveolar Macrophages by Inhibition of the Long Terminal Repeat

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

doi:10.1165/rcmb.2008-0063oc

Cited by 4 publications

(4 citation statements)

References 66 publications

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“…These data support previous observations of HIV‐1 replication in lungs . Previous studies have demonstrated that HIV‐1 replicates in alveolar macrophages , others showed that CCR5 + CD4 + BAL T cells support replication . These results show in some people an elevation of HIV‐1 RNA concentration in BAL fluid compared to serum, which supports compartmentalised local viral replication in human lungs.…”

Section: Discussionsupporting

confidence: 90%

Relationship between chemokine receptor expression, chemokine levels and HIV‐1 replication in the lungs of persons exposed to Mycobacterium tuberculosis

et al. 2012

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Increased susceptibility to tuberculosis following HIV-1 seroconversion contributes significantly to the tuberculosis epidemic in sub-saharan Africa. Lung specific mechanisms underlying the interaction between HIV-1 and Mycobacterium (M.) tuberculosis infection are incompletely understood. This study addressed the effect of HIV-1 and latent M. tuberculosis infection on viral-entry receptors and ligands in bronchoalveolar lavage (BAL). Median fluorescence intensity (MFI) of entry receptor expression was measured by multiparameter flow cytometry and chemokine expression by multiplex bead array. Irrespective of HIV-1 status, BAL T-cells expressed higher MFI for the beta-chemokine receptor (CCR)5 than peripheral blood T-cells (p<0.001), in particular the CD8+ T-cells of HIV-1 infected persons showed elevated CCR5 expression (p=0.026). The concentration of BAL CCR5 ligands, regulated upon activation normal T-cell expressed and secreted (RANTES; p<0.001) and macrophage inflammatory protein (MIP)-1β (p=0.004) were elevated in the BAL of HIV-1 infected persons compared to controls. CCR5 expression and RANTES concentration correlated strongly with HIV-1 viral load in BAL. By contrast these alterations were not associated with M. tuberculosis sensitization in vivo nor did M. tuberculosis infection of BAL cells ex vivo change RANTES expression. These data suggest ongoing HIV-1 replication predominantly drives local pulmonary CCR5+ T-cell activation in HIV/latent M. tuberculosis co-infection.

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Section: Discussionsupporting

confidence: 90%

Relationship between chemokine receptor expression, chemokine levels and HIV‐1 replication in the lungs of persons exposed to Mycobacterium tuberculosis

et al. 2012

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“…To assess the effect of HIV1 infection on AM production of IL-23, we used an established model of in vitro infection of AM with an HIV1 laboratory strain, JRFL [ 30 ]. IL-23 expression in JFRL-infected AM was compared to IL-23 expression in uninfected control AM.…”

Section: Resultsmentioning

confidence: 99%

“…HIV1 − AM (2-3 × 10 5 /well) were infected with the HIV-1 laboratory strain, JRFL, at 10 3 median tissue culture infectious doses (TCID50) per well, a dose known to infect cells of monocytic origin [ 30 ]. After 12 days of incubation at 37°C, the cells were washed and the RNA was isolated.…”

Section: Methodsmentioning

confidence: 99%

The Role of Interleukin-23 in the Early Development of Emphysema in HIV1⁺Smokers

Crystal

Kaner

2016

Journal of Immunology Research

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Rationale. Matrix metalloproteinase-9 (MMP-9) expression is upregulated in alveolar macrophages (AM) of HIV1+ smokers who develop emphysema. Knowing that lung epithelial lining fluid (ELF) of HIV1+ smokers contains increased levels of inflammatory cytokines compared to HIV1− smokers, we hypothesized that upregulation of lung cytokines in HIV1+ smokers may be functionally related to increased MMP-9 expression. Methods. Cytokine arrays evaluated cytokine protein levels in ELF obtained from 5 groups of individuals: HIV1− healthy nonsmokers, HIV1− healthy smokers, HIV1− smokers with low diffusing capacity (DLCO), HIV1+ nonsmokers, and HIV1+ smokers with low DLCO. Results. Increased levels of the Th17 related cytokine IL-23 were found in HIV1− smokers with low DLCO and HIV1+ smokers and nonsmokers. Relative IL-23 gene expression was increased in AM of HIV1+ individuals, with greater expression in AM of HIV1+ smokers with low DLCO. Infection with HIV1 in vitro induced IL-23 expression in normal AM. IL-23 stimulation of AM/lymphocyte cocultures in vitro induced upregulation of MMP-9. Lung T lymphocytes express receptor IL-23R and interact with AM in order to upregulate MMP-9. Conclusion. This mechanism may contribute to the increased tissue destruction in the lungs of HIV1+ smokers and suggests that Th17 related inflammation may play a role.

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“…Around 2007 some clinical trials resulted in no protection against HIV, while other clinical trials indicated possible problems involving previous Ad5 infection, emerging evidence showed that previous exposure to adenovirus could impair vaccine efficacy ( Steinbrook, 2007 ; Quirk et al, 2008 ; Sekaly, 2008 ; Yu et al, 2008 ). Even worse, Ad5 seropositive individuals vaccinated could have a more permissive environment for HIV infection ( Perreau et al, 2008 ; Benlahrech et al, 2009 ; D’Souza and Frahm, 2010 ; Hu et al, 2014 ), despite some controversial results ( O’Brien et al, 2009 ; Curlin et al, 2011 ; Kaner et al, 2012 ). In spite of the increased susceptibility to HIV infection, later analysis showed no difference in disease progression between Ad5 vaccinated and placebo groups ( Fitzgerald et al, 2011 ).…”

Section: Use Of Adenoviral Vectors As Vaccinesmentioning

confidence: 99%

The use of adenoviral vectors in gene therapy and vaccine approaches

et al. 2022

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Adenovirus was first identified in the 1950s and since then this pathogenic group of viruses has been explored and transformed into a genetic transfer vehicle. Modification or deletion of few genes are necessary to transform it into a conditionally or non-replicative vector, creating a versatile tool capable of transducing different tissues and inducing high levels of transgene expression. In the early years of vector development, the application in monogenic diseases faced several hurdles, including short-term gene expression and even a fatality. On the other hand, an adenoviral delivery strategy for treatment of cancer was the first approved gene therapy product. There is an increasing interest in expressing transgenes with therapeutic potential targeting the cancer hallmarks, inhibiting metastasis, inducing cancer cell death or modulating the immune system to attack the tumor cells. Replicative adenovirus as vaccines may be even older and date to a few years of its discovery, application of non-replicative adenovirus for vaccination against different microorganisms has been investigated, but only recently, it demonstrated its full potential being one of the leading vaccination tools for COVID-19. This is not a new vector nor a new technology, but the result of decades of careful and intense work in this field.

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Adenovirus Vectors Block Human Immunodeficiency Virus–1 Replication in Human Alveolar Macrophages by Inhibition of the Long Terminal Repeat

Cited by 4 publications

References 66 publications

Relationship between chemokine receptor expression, chemokine levels and HIV‐1 replication in the lungs of persons exposed to Mycobacterium tuberculosis

Relationship between chemokine receptor expression, chemokine levels and HIV‐1 replication in the lungs of persons exposed to Mycobacterium tuberculosis

The Role of Interleukin-23 in the Early Development of Emphysema in HIV1⁺Smokers

The use of adenoviral vectors in gene therapy and vaccine approaches

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Adenovirus Vectors Block Human Immunodeficiency Virus–1 Replication in Human Alveolar Macrophages by Inhibition of the Long Terminal Repeat

Cited by 4 publications

References 66 publications

Relationship between chemokine receptor expression, chemokine levels and HIV‐1 replication in the lungs of persons exposed to Mycobacterium tuberculosis

Relationship between chemokine receptor expression, chemokine levels and HIV‐1 replication in the lungs of persons exposed to Mycobacterium tuberculosis

The Role of Interleukin-23 in the Early Development of Emphysema in HIV1+Smokers

The use of adenoviral vectors in gene therapy and vaccine approaches

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Product

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The Role of Interleukin-23 in the Early Development of Emphysema in HIV1⁺Smokers