The lungs as anatomical reservoirs of HIV infection

Costiniuk, Cecilia T.; Jenabian, Mohammad-Ali

doi:10.1002/rmv.1772

Cited by 63 publications

(71 citation statements)

References 139 publications

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“…Lung alveolar macrophages, isolated from bronchoalveolar lavage (BAL), are targeted by HIV-1 with implications both for local tissue damage and viral reservoir formation (Costiniuk and Jenabian, 2014). In the SIV macaque model, alveolar macrophages were SIV RNA + within 10 days post-infection onwards, demonstrating rapid seeding of lung tissue, and were the major cell type infected (Li et al, 2015).…”

Section: Macrophages As Viral Tissue Reservoirsmentioning

confidence: 99%

Macrophages and HIV-1: An Unhealthy Constellation

Sattentau

Stevenson

2016

Cell Host & Microbe

145

125

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Lentiviruses have a long-documented association with macrophages. Abundant evidence exists for in vitro and, in a tissue-specific manner, in vivo infection of macrophages by the primate lentiviruses HIV-1 and SIV. However, macrophage contribution to aspects of HIV-1 and SIV pathogenesis, and their role in viral persistence in individuals on suppressive antiretroviral therapy remains unclear. Here we discuss recent evidence implicating macrophages in HIV-1-mediated disease, and highlight directions for further investigation.

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Section: Macrophages As Viral Tissue Reservoirsmentioning

confidence: 99%

Macrophages and HIV-1: An Unhealthy Constellation

Sattentau

Stevenson

2016

Cell Host & Microbe

145

125

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“…HIV-infected macrophages are one such cell type worth consideration and several excellent reviews have recently elaborated on this subject (Costiniuk and Jenabian, 2014; Dey et al , 2012; Stevenson, 2014; Tan and Sattentau, 2013; Watters et al , 2013). Infected macrophages have been found at low but measurable frequencies in lung and duodenal tissue of patients on ART with undetectable plasma virus (Cribbs et al , 2015; Zalar et al , 2010) and in brain tissues of SIV-infected macaques on ART (Clements et al , 2002).…”

mentioning

confidence: 99%

Role of the macrophage in HIV-associated neurocognitive disorders and other comorbidities in patients on effective antiretroviral treatment

Rappaport

Volsky

2015

J. Neurovirol.

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Combination antiretroviral therapy (ART) has altered the outcomes of HIV infection in treated populations by greatly reducing the incidence of opportunistic infections, cancer, and HIV-associated dementia. Despite these benefits, treated patients remain at high risk of chronic diseases affecting peripheral organs and brain. Generally, these morbidities are attributed to persistence of latent HIV in resting T cells, chronic inflammation, and metabolic effects of ART. This review makes the case that monocytes/macrophages warrant attention as persistent reservoirs of HIV under ART, source of systemic and brain inflammation, and important targets for HIV eradication to control chronic HIV diseases.

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“…T cells, and fibroblasts (30,31) in the lung can harbor HIV-1. Although the frequency of infected CD4 1 T cells in BAL is not higher than in blood (32), alveolar macrophages, particularly small ones, are preferentially infected, providing a focus of HIV-1 infection in the lung that drives the influx of HIV-1-specific T cells (33).…”

mentioning

confidence: 99%

Lymphocytic Alveolitis Is Associated with the Accumulation of Functionally Impaired HIV-Specific T Cells in the Lung of Antiretroviral Therapy–Naive Subjects

Neff¹,

Chain²,

MaWhinney³

et al. 2015

Am J Respir Crit Care Med

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Rationale: Lymphocytic alveolitis in HIV-1-infected individuals is associated with multiple pulmonary complications and a poor prognosis. Although lymphocytic alveolitis has been associated with viremia and an increased number of CD8 1 T cells in the lung, its exact cause is unknown.Objectives: To determine if HIV-1-specific T cells are associated with lymphocytic alveolitis in HIV-1-infected individuals.Methods: Using blood and bronchoalveolar lavage (BAL) cells from normal control subjects and untreated HIV-1-infected individuals, we examined the frequency and functional capacity of HIV-1-specific T cells. Measurements and Main Results:We found that HIV-1-specific T cells were significantly elevated in the BAL compared with blood of HIV-1-infected individuals and strongly correlated with T-cell alveolitis. Expression of Ki67, a marker of in vivo proliferation, was significantly reduced on HIV-1-specific T cells in BAL compared with blood, suggesting a diminished proliferative capacity. In addition, HIV-1-specific CD4 1 and CD8 1 T cells in BAL had higher expression of programmed death 1 (PD-1) and lower cytotoxic T-lymphocyte antigen 4 (CTLA-4) expression than those in the blood. A strong correlation between PD-1, but not CTLA-4, and HIV-1-specific T-cell proliferation was seen, and blockade of the PD-1/PD-L1 pathway augmented HIV-1-specific T-cell proliferation, suggesting that the PD-1 pathway was the main cause of reduced proliferation in the lung.Conclusions: These findings suggest that alveolitis associated with HIV-1 infection is caused by the recruitment of HIV-1-specific CD4 1 and CD8 1 T cells to the lung. These antigen-specific T cells display an impaired proliferative capacity that is caused by increased expression of PD-1.

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The lungs as anatomical reservoirs of HIV infection

Cited by 63 publications

References 139 publications

Macrophages and HIV-1: An Unhealthy Constellation

Macrophages and HIV-1: An Unhealthy Constellation

Role of the macrophage in HIV-associated neurocognitive disorders and other comorbidities in patients on effective antiretroviral treatment

Lymphocytic Alveolitis Is Associated with the Accumulation of Functionally Impaired HIV-Specific T Cells in the Lung of Antiretroviral Therapy–Naive Subjects

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