Cigarette smoke and HIV synergistically affect lung pathology in cynomolgus macaques

Chand, Hitendra S.; Guillamet, Rodrigo Vazquez; Royer, Christopher M.; Rudolph, Karin; Mishra, Neerad C.; Singh, Shashi P.; Hussain, Shah S.; Barrett, Edward G.; Callen, Shannon; Byrareddy, Siddappa N.; Guillamet, M Cristina Vazquez; Abukhalaf, Jawad; Sheybani, Aryaz; Exil, Vernat; Raizada, Veena; Agarwal, Hemant; Nair, Madhavan; Villinger, François; Buch, Shilpa; Sopori, Mohan L.

doi:10.1172/jci121935

Cited by 24 publications

(34 citation statements)

References 47 publications

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“…We have previously demonstrated that HIV-and SIV-infected lungs from humans and monkeys, respectively, contain HIV-gp120 immunoreactive cells (11). More recently, we have shown that a significant number of airway and alveolar epithelial cells in SHIV-infected CMs are HIV-gp120-positive and the number of these cells are essentially doubled in SHIV+CS-exposed lungs (19). To determine that HIV replicates in airway epithelial cells in-vivo, we performed RNA FISH by RNAScope® technology (Advanced Cell Diagnostics, Biotechne Inc.) using commercially available HIVgag-pol probes (ACD, Bioteche Inc.).…”

Section: Hiv Rna Is Present In Lung Epithelial Cells From Sihv-infectmentioning

confidence: 87%

“…Next, we analyzed the CD4 and CXCR4 receptor expression in the lung epithelium of nonhuman primates. Archived lung tissues from the cynomologus macaques (CMs) that were exposed to CS for 27 weeks and/or infected with SHIV at 11 th week to obtain 4 experimental groups: fresh air control (FA), CS-exposed, SHIV-infected, and CS+SHIV, as described recently (19). All SHIV-infected macaques received daily injections of cART (Tenofovir and Emtrictabine) starting at 2 weeks post infection until euthanasia.…”

Section: Hiv Co-receptors Are Expressed In-vivo In Lung Epithelium Ofmentioning

confidence: 99%

“…For immunohistochemical staining, deparaffinized and hydrated lung tissue sections were washed in 0.05% v Brij-35 in PBS (pH 7.4) and immunostained for antigen expression as described previously (19). Briefly, the antigens were unmasked by steaming the sections in 10 mM Citrate buffer (pH 6.0) followed by incubation in a blocking solution containing 3% BSA, 1% Gelatin and 1% normal donkey serum with 0.1% Triton X-100 and 0.1% Saponin and were stained with antibodies to CD4 (Abcam, #ab133616), CXCR4 (Abcam, #ab181020), CCR5 (Abcam, #ab11466), HIV-Tat (Abcam, #ab63957) and pan-CK (#4545, Cell Signaling Technologies, Danvers, MA).…”

Section: Immunostaining and Fluorescent Imaging Analysismentioning

confidence: 99%

“…Similarly, X4-tropic, but not R5-tropic, HIV impairs epithelial barrier integrity in NHBE cells (18). Also, cynomolgus monkeys (CMs) infected with simian-adapted HIV (SHIV) contain large number of mucus containing goblet cells and a significant percentage of SHIV-infected airway epithelial cells are HIV-gp120-positive (19); however, whether HIV productively infects airway epithelial cells is still debatable (18,20). This question can be answered definitively, if the HIV-infected bronchial epithelial cells are shown to contain activatable integrated HIV provirus.…”

Section: Introductionmentioning

confidence: 99%

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Lung Bronchial Epithelial Cells are HIV Targets for Proviral Genomic Integration

Devadoss

Acharya

et al. 2020

Preprint

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In the era of highly active anti-retroviral therapy (HAART), obstructive lung diseases (OLDs) are common among the people living with HIV (PLWH); however, the mechanism by which HIV induces OLDs is unclear. Although human bronchial epithelial cells (HBECs) express HIV coreceptors and are critical in regulating lung immune responses, their role in transmitting HIV remains unclear. Herein, we present evidence that HIV-1 infects normal HBECs and the viral DNA is integrated in the genome to establish the viral latency. To prove that HIV productively infects HBECs, we demonstrate: (a) along with CXCR4, HBECs express the HIV-receptor CD4, and are induced to express CCR5 by IL-13 treatment; (b) following infection with HIV, HBECs produce HIV-p24 and contain the latent HIV provirus, which is activated by endotoxin and/or vorinostat; (c) DNA from HIV-1 infected HBECs contains the HIV-specific gag and nef genes, along with Alu sequences, confirming the integration of HIV in the host DNA; (d) the lung epithelial cells of HIV-infected subjects and SHIV-infected cynomolgus macaques are positive for HIV-specific transcripts. Thus, these studies suggest that HIV establishes latency in lung epithelial cells, making them potential HIV reservoirs. The long-living lung epithelial cells, activated by commonly encountered lung infections, might represent an ideal HIV target/reservoir, contributing to OLDs and other HIV-associated lung comorbidities.

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Section: Hiv Rna Is Present In Lung Epithelial Cells From Sihv-infectmentioning

confidence: 87%

Section: Hiv Co-receptors Are Expressed In-vivo In Lung Epithelium Ofmentioning

confidence: 99%

Section: Immunostaining and Fluorescent Imaging Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Lung Bronchial Epithelial Cells are HIV Targets for Proviral Genomic Integration

Devadoss

Acharya

et al. 2020

Preprint

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“…Here, more than 40% of patients were smokers. Synergistic effects of tobacco and HIV [24] in promoting chronic bronchitis and pro-COPD changes in the lung [25] have been demonstrated. Moreover, high rates of viral documentation within airways of COPD patients both at stable state and during exacerbation have been reported [26].…”

Section: Discussionmentioning

confidence: 99%

Respiratory virus-associated infections in HIV-infected adults admitted to the intensive care unit for acute respiratory failure: a 6-year bicenter retrospective study (HIV-VIR study)

Elabbadi

Pichon

Visseaux

et al. 2020

Ann. Intensive Care

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Introduction Acute respiratory failure is the main reason for admission to the intensive care unit (ICU) in HIV-infected adults. There is little data about the epidemiology of respiratory viruses in this population. Methods HIV-infected adults admitted to two intensive care units over a 6-year period for an acute respiratory failure and explored for respiratory viruses with multiplex polymerase chain reaction (mPCR) were retrospectively selected. Objectives were to describe the prevalence of respiratory viruses, coinfections with non-viral pathogens, and hospital outcome. Results A total of 123 episodes were included. An HIV infection was newly diagnosed in 9% of cases and 72% of the population were on antiretroviral therapy. Real-time mPCR tests identified at least one respiratory virus in the respiratory tract of 33 (27%) patients, but with a non-viral copathogen in two-thirds of cases. Rhinovirus was predominant, documented in 15 patients, followed by Influenza and Respiratory Syncytial Viruses (both n = 6). The prevalence of respiratory virus-associated infection did not vary along with the level of the CD4 T-cell deficiency, except for Rhinovirus which was more prevalent in patients with a CD4 lymphocyte count below 200 cells/µL (n = 13 (20%) vs. n = 2 (4%), p < 0.01). In multivariate analysis, respiratory virus-associated infection was not associated with a worse prognosis. Conclusions Viruses are frequently identified in the respiratory tract of HIV-infected patients with acute respiratory failure that requires ICU admission, but with a non-viral copathogen in two-thirds of cases. Rhinovirus is the predominant viral specie; its prevalence is highest in patients with a CD4 lymphocyte count below 200 cells/µL.

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Tight junctions in the development of asthma, chronic rhinosinusitis, atopic dermatitis, eosinophilic esophagitis, and inflammatory bowel diseases

Sugita

Kabashima

2020

Journal of Leukocyte Biology

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This review focuses on recent developments related to asthma, chronic rhinosinusitis, atopic dermatitis (AD), eosinophilic esophagitis, and inflammatory bowel diseases (IBD), with a particular focus on tight junctions (TJs) and their role in the pathogenetic mechanisms of these diseases. Lung, skin, and intestinal surfaces are lined by epithelial cells that interact with environmental factors and immune cells. Therefore, together with the cellular immune system, the epithelium performs a pivotal role as the first line physical barrier against external antigens. Paracellular space is almost exclusively sealed by TJs and is maintained by complex protein-protein interactions. Thus, TJ dysfunction increases paracellular permeability, resulting in enhanced flux across TJs. Epithelial TJ dysfunction also causes immune cell activation and contributes to the pathogenesis of chronic lung, skin, and intestinal inflammation. Characterization of TJ protein alteration is one of the key factors for enhancing our understanding of allergic diseases as well as IBDs. Furthermore, TJ-based epithelial disturbance can promote immune cell behaviors, such as those in dendritic cells, Th2 cells, Th17 cells, and innate lymphoid cells (ILCs), thereby offering new insights into TJ-based targets. The purpose of this review is to illustrate how TJ dysfunction can lead to the disruption of the immune homeostasis in barrier tissues and subsequent inflammation.This review also highlights the various TJ barrier dysfunctions across different organ sites, which would help to develop future drugs to target allergic diseases and IBD.

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Cigarette smoke and HIV synergistically affect lung pathology in cynomolgus macaques

Cited by 24 publications

References 47 publications

Lung Bronchial Epithelial Cells are HIV Targets for Proviral Genomic Integration

Lung Bronchial Epithelial Cells are HIV Targets for Proviral Genomic Integration

Respiratory virus-associated infections in HIV-infected adults admitted to the intensive care unit for acute respiratory failure: a 6-year bicenter retrospective study (HIV-VIR study)

Tight junctions in the development of asthma, chronic rhinosinusitis, atopic dermatitis, eosinophilic esophagitis, and inflammatory bowel diseases

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