The growth and the control of human immunodeficiency virus in the lung: implications for highly active antiretroviral therapy

White,; Agostini, Carlo; Israel-Biet, Dominique; Semenzato, Gianpietro; Clarke,

doi:10.1046/j.1365-2362.1999.00550.x

Cited by 23 publications

(27 citation statements)

References 63 publications

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“…Activated MMPs also exert significant control over inflammation, modulating the recruitment of leukocytes into the lung [7,12]. Since HIV1 ؉ smokers have a higher incidence of emphysema than HIV1 Ϫ smokers and since alveolar macrophages are known to be activated in HIV1 ϩ individuals [13][14][15][16][17][18][19][20] and in HIV1 Ϫ smokers [8], we hypothesized that AM of HIV1 ϩ smokers may up-regulate the expression of MMPs to a higher extent than HIV1 -smokers.…”

Section: Introductionmentioning

confidence: 99%

Up-regulation of alveolar macrophage matrix metalloproteinases in HIV1+ smokers with early emphysema

Kaner

Santiago

Crystal

2009

Journal of Leukocyte Biology

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HIV1(+) smokers develop emphysema at an earlier age and with a higher incidence than HIV1(-) smokers. Since human alveolar macrophages (AMs) are capable of producing proteases that degrade extracellular matrix components, we hypothesized that up-regulation of AM matrix metalloproteinases may be associated with the emphysema of HIV1(+) smokers. Microarray analysis was used to screen which matrix metalloproteinases (MMPs) genes were expressed by AM of HIV1(+) smokers with early emphysema. For each of the MMP genes expressed (MMP-1, -2, -7, -9, -10, -12 and -14), TaqMan PCR was used to quantify the relative expression in AM from four groups of individuals: HIV1(-) healthy nonsmokers, HIV1(-) healthy smokers, HIV1(-) smokers with early emphysema, and HIV1(+) smokers with early emphysema. While AM gene expression of MMPs was higher in HIV1(-) individuals with emphysema in comparison with HIV1(-) healthy smokers, for the majority of the MMPs (-1, -7, -9, and -12), AM expression from HIV1(+) smokers with early emphysema was significantly higher than in HIV1(-) smokers with early emphysema. HIV1(+) individuals with early emphysema also had higher levels of epithelial lining fluid (ELF) MMPs (-2, -7, -9, and -12) than the 3 HIV1(-) groups. ELF MMP (-2,-7,-9, and -12) levels were similar in HIV1(+) nonsmokers compared with HIV1(-) nonsmokers. Interestingly, the active forms of MMP-2, -9, and -12 were exclusively detected in ELF from HIV1(+) individuals with early emphysema. Since the activities of the up-regulated AM MMPs include collagenases, gelatinases, matrilysins, and elastase, these data suggest that up-regulated AM MMP genes and activation of MMP proteins may contribute to the emphysema of HIV1(+) individuals who smoke.

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Section: Introductionmentioning

confidence: 99%

Up-regulation of alveolar macrophage matrix metalloproteinases in HIV1+ smokers with early emphysema

Kaner

Santiago

Crystal

2009

Journal of Leukocyte Biology

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“…THE LUNG IS AN IMPORTANT RESERVOIR of HIV and a site for HIV replication (44). HIV is uniformly detected in alveolar macrophages of infected pediatric patients and in the majority of adult patients (30).…”

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confidence: 99%

Proteomic landscape of bronchoalveolar lavage fluid in human immunodeficiency virus infection

Nguyen

Gharib

Crothers

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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The lung is an important reservoir of human immunodeficiency virus (HIV). Individuals infected with HIV are more prone to pulmonary infections and chronic lung disorders. We hypothesized that comprehensively profiling the proteomic landscape of bronchoalveolar lavage fluid (BALF) in patients with HIV would provide insights into how this virus alters the lung milieu and contributes to pathogenesis of HIV-related lung diseases. BALF was obtained from five HIV-negative (HIV(-)) and six asymptomatic HIV-positive (HIV(+)) subjects not on antiretroviral therapy. Each sample underwent shotgun proteomic analysis based on HPLC-tandem mass spectrometry. Differentially expressed proteins between the groups were identified using statistical methods based on spectral counting. Mechanisms of disease were explored using functional annotation to identify overlapping and distinct pathways enriched between the BALF proteome of HIV(+) and HIV(-) subjects. We identified a total of 318 unique proteins in BALF of HIV(-) and HIV(+) subjects. Of these, 87 were differentially up- or downregulated between the two groups. Many of these differentially expressed proteins are known to interact with key HIV proteins. Functional analysis of differentially regulated proteins implicated downregulation of immune responses in lungs of HIV(+) patients. Combining shotgun proteomic analysis with computational methods demonstrated that the BALF proteome is significantly altered during HIV infection. We found that immunity-related pathways are underrepresented in HIV(+) patients. These findings implicate mechanisms whereby HIV invokes local immunosuppression in the lung and increases the susceptibility of HIV(+) patients to develop a wide range of infectious and noninfectious pulmonary diseases.

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“…In spite of highly active antiretroviral therapy (HAART) suppression of HIV-1 replication in T cells, various reservoirs, including AMs, dendritic cells, and other monocyte-derived tissue macrophages continue to harbor the virus (3,4). We have previously shown that if AMs are infected with an E1 2 E3 2 adenovirus (Ad) gene transfer vector before in vitro HIV-1 infection, subsequent replication of HIV-1 by the AM is markedly suppressed independently of the transgene in the Ad vector (5).…”

mentioning

confidence: 99%

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

Kaner

Santiago²,

Rahaghi³

et al. 2010

Am J Respir Cell Mol Biol

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The growth and the control of human immunodeficiency virus in the lung: implications for highly active antiretroviral therapy

Cited by 23 publications

References 63 publications

Up-regulation of alveolar macrophage matrix metalloproteinases in HIV1+ smokers with early emphysema

Up-regulation of alveolar macrophage matrix metalloproteinases in HIV1+ smokers with early emphysema

Proteomic landscape of bronchoalveolar lavage fluid in human immunodeficiency virus infection

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

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