Low CD4 T-cell counts despite low levels of circulating HIV: Insights from the comparison of HIV-1 infected patients with a discordant response to antiretroviral therapy to patients with untreated advanced HIV-2 disease

Albuquerque, Adriana S.; Foxall, Russell B.; Cortesão, Catarina S.; Soares, Rui; Doroana, Manuela; Ribeiro, Alice; Lucas, Margarida; Antúnes, Francisco; Victorino, Rui M. M.; Sousa, Ana E.

doi:10.1016/j.clim.2007.07.001

Cited by 6 publications

(2 citation statements)

References 40 publications

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“…Of note, the persistent immune activation of our patient featured an AIDS-like immunological profile (33–35). CGD is typically associated with an inflammatory and hyper-activated state (3, 32, 36, 37).…”

Section: Discussionmentioning

confidence: 64%

Major CD4 T-Cell Depletion and Immune Senescence in a Patient with Chronic Granulomatous Disease

et al. 2017

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Chronic granulomatous disease (CGD) results from primary defects in phagocytic reactive oxygen species (ROS) production. T-cell evaluation is usually neglected during patients’ follow-up, although T-cell depletion has been reported in CGD through unknown mechanisms. We describe here a 36-year-old patient with X-linked CGD with severe CD4 T-cell depletion <200 CD4 T-cells/μl, providing insights into the mechanisms that underlie T-cell loss in the context of oxidative burst defects. In addition to the typical infections, the patient featured a progressive T-cell loss associated with persistent lymphocyte activation, expansion of interleukin (IL)-17-producing CD4 T-cells, and impaired thymic activity, leading to a reduced replenishment of the T-cell pool. A relative CD4 depletion was also found at the gut mucosal level, although no bias to IL-17-production was documented. This immunological pattern of exhaustion of immune resources favors prompt, potentially curative, therapeutic interventions in CGD patients, namely, stem-cell transplantation or gene therapy. Moreover, this clinical case raises new research questions on the interplay of ROS production and T-cell homeostasis and immune senescence.

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Section: Discussionmentioning

confidence: 64%

Major CD4 T-Cell Depletion and Immune Senescence in a Patient with Chronic Granulomatous Disease

et al. 2017

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“…Autophagy initiation can also be inhibited through the bcl-2–beclin-1 interaction [ 84 ]. There are several publications demonstrating changes in bcl-2 in the presence of ART, either in PBMC from PLWH or in cancer cell models, but the effects of the antiretrovirals are varied [ 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 ], suggesting a drug-, cell- and/or disease process type-specific effect of antiretrovirals on bcl-2. To our knowledge, there are no studies linking antiretroviral drugs to autophagy changes through changes in bcl-2.…”

Section: Discussionmentioning

confidence: 99%

HIV Nef and Antiretroviral Therapy Have an Inhibitory Effect on Autophagy in Human Astrocytes that May Contribute to HIV-Associated Neurocognitive Disorders

Cheney

Guzik

Macaluso

et al. 2020

Cells

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A significant number of people living with HIV (PLWH) develop HIV-associated neurocognitive disorders (HAND) despite highly effective antiretroviral therapy (ART). Dysregulated macroautophagy (autophagy) is implicated in HAND pathogenesis. The viral protein Nef, expressed even with suppressive ART, and certain antiretrovirals affect autophagy in non-CNS cells. Astrocytes, vital for CNS microenvironment homeostasis and neuronal health, require autophagy for their own homeostasis. We hypothesized that extracellular Nef and/or ART impact astrocyte autophagy, thus contributing to HAND. We studied in-bulk and selective autophagic flux in primary human astrocytes treated with extracellular Nef and/or a combination of tenofovir+emtricitabine+raltegravir (ART) using Western blotting, a tandem fluorescent LC3 reporter, and transmission electron microscopy/morphometry. We show that after 24 h treatment, Nef and ART decrease autophagosomes through different mechanisms. While Nef accelerates autophagosome degradation without inducing autophagosome formation, ART inhibits autophagosome formation. Combination Nef+ART further depletes autophagosomes by inducing both abnormalities. Additionally, extracellular Nef and/or ART inhibit lysosomal degradation of p62, indicating Nef and/or ART affect in-bulk and selective autophagy differently. Dysregulation of both autophagic processes is maintained after 7 days of Nef and/or ART treatment. Persistent autophagy dysregulation due to chronic Nef and/or ART exposure may ultimately result in astrocyte and neuronal dysfunction, contributing to HAND.

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Increased frequency of CD25dimCD4+ T-cells in HIV-2 infection, a naturally occurring attenuated form of HIV-1

Foxall¹,

Soares²,

Albuquerque³

et al. 2008

Clinical Immunology

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Low CD4 T-cell counts despite low levels of circulating HIV: Insights from the comparison of HIV-1 infected patients with a discordant response to antiretroviral therapy to patients with untreated advanced HIV-2 disease

Cited by 6 publications

References 40 publications

Major CD4 T-Cell Depletion and Immune Senescence in a Patient with Chronic Granulomatous Disease

Major CD4 T-Cell Depletion and Immune Senescence in a Patient with Chronic Granulomatous Disease

HIV Nef and Antiretroviral Therapy Have an Inhibitory Effect on Autophagy in Human Astrocytes that May Contribute to HIV-Associated Neurocognitive Disorders

Increased frequency of CD25dimCD4+ T-cells in HIV-2 infection, a naturally occurring attenuated form of HIV-1

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