Association of Viral Persistence and Atherosclerosis in Adults With Treated HIV Infection

McLaughlin, Megan M.; Ma, Yifei; Scherzer, Rebecca; Rahalkar, Smruti; Martin, Jeffrey N.; Mills, Claire; Milush, Jeffrey M.; Deeks, Steven G.; Hsue, Priscilla Y.

doi:10.1001/jamanetworkopen.2020.18099

Cited by 30 publications

(27 citation statements)

References 69 publications

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“…T-cells are independently associated with progression of carotid intima-media thickness and incident plaque development in PLWH. 50 Lastly, standardizing the methodology of PET imaging acquisition and evaluation would facilitate multicenter study across populations.…”

Section: Application Of Nuclear Imaging To Understand Neurohivmentioning

confidence: 99%

Investigating vascular diseases in people living with HIV by nuclear imaging

Chan

Spudich

2022

Journal of Nuclear Cardiology

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Section: Application Of Nuclear Imaging To Understand Neurohivmentioning

confidence: 99%

Investigating vascular diseases in people living with HIV by nuclear imaging

Chan

Spudich

2022

Journal of Nuclear Cardiology

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“…Finally, we used plaque assay to confirm the efficiency of the siRNA approach in preventing plaques formed in MRC-5 monolayers as a result of hCoV-229E-infection. The plaque reduction neutralization test (PRNT) is considered a "gold standard" in the evaluation of antiviral strategies used against SARS-CoV-2 infections (Padoan et al, 2020;Perera et al, 2020;Xie et al, 2020) and other viral infections (McLaughlin et al, 2020;Yau et al, 2020). Using the PLANA-delivered combination of siRNAs targeting S-protein and E-protein completely eliminated plaques that were observed in non-treated cell cultures (Figure 5).…”

Section: Antiviral Effectmentioning

confidence: 99%

Suppression of Human Coronavirus 229E Infection in Lung Fibroblast Cells via RNA Interference

Aliabadi

Totonchy

Mahdipoor

et al. 2021

Front. Nanotechnol.

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Despite extensive efforts to repurpose approved drugs, discover new small molecules, and develop vaccines, COVID-19 pandemic is still claiming victims around the world. The current arsenal of antiviral compounds did not perform well in the past viral infections (e.g., SARS), which casts a shadow of doubt for use against the new SARS-CoV-2. Vaccines should offer the ultimate protection; however, there is limited information about the longevity of the generated immunity and the protection against possible mutations. This study uses Human Coronavirus 229E as a model coronavirus to test the hypothesis that effective delivery of virus-specific siRNAs to infected cells will result in lower viral load and reduced cell death. Two different categories of nucleic acid delivery systems, Peptide/Lipid-Associated Nucleic Acids (PLANAs) and lipophilic polymers, were investigated for their toxicity in human lung fibroblast cells and their ability to deliver specific siRNAs targeting Spike and Envelope proteins in order to prevent cell death in infected cells. Selected siRNAs were effectively delivered to human lung fibroblast cells with negligible toxicity. Cell death due to viral infection was significantly reduced with individual and combinatorial silencing of selected viral proteins. The combinatorial silencing of Spike and Envelope proteins restored the cell viability completely and eliminated plaques in the investigated system. Our cell culture data indicate promising results for the RNAi based approach as an alternative antiviral treatment.

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“…Human immunodeficiency virus (HIV) infection greatly increases the risk of atherosclerosis (AS) associated cardiovascular disease (CVD), which is a leading cause of morbidity and mortality in persons living with HIV (PLWH) (1)(2)(3)(4). Several factors contribute to this elevated risk of AS.…”

Section: Introductionmentioning

confidence: 99%

“…Chronic human immunodeficiency virus (HIV) infection increases the risk of atherosclerosis (AS) associated cardiovascular disease (CVD), which is a leading cause of morbidity in persons living with HIV (PLWH) (1)(2)(3)(4). PLWH have an increased prevalence of risk factors for AS (5)(6)(7)(8)(9), some of which are driven by the off-target effects of antiretroviral drugs (9,10).…”

Section: Introductionmentioning

confidence: 99%

Executable models of immune signaling pathways in HIV-associated atherosclerosis

Palshikar

Palli

Tyrell

et al. 2022

Preprint

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Background: Atherosclerosis (AS)-associated cardiovascular disease is an important cause of mortality in an aging population of people living with HIV (PLWH). This elevated risk of atherosclerosis has been attributed to viral infection, prolonged usage of anti-retroviral therapy, and subsequent chronic inflammation. Methods: To investigate dysregulated immune signaling in PLWH with and without AS, we sequenced 9368 peripheral blood mononuclear cells (PBMCs) from 8 PLWH, 4 of whom also had atherosclerosis (AS+). To develop executable models of signaling pathways that drive cellular states in HIV-associated atherosclerosis, we developed the single-cell Boolean Omics Network Invariant Time Analysis (scBONITA) algorithm. ScBONITA (a) uses single-cell RNA sequencing data to infer Boolean rules for topologically characterized networks, (b) prioritizes genes based on their impact on signaling, (c) performs pathway analysis, and (d) maps sequenced cells to characteristic signaling states. We used scBONITA to identify dysregulated pathways in different cell-types from AS+ PLWH and AS- PLWH. To compare our findings with pathways associated with HIV infection, we used scBONITA to analyze a publicly available dataset of PBMCs from subjects before and after HIV infection. Additionally, the executable Boolean models characterized by scBONITA were used to analyze observed cellular states corresponding to the steady states of signaling pathways Results: We identified an increased subpopulation of CD8+ T cells and a decreased subpopulation of monocytes in AS+ PLWH. Dynamic modeling of signaling pathways and pathway analysis with scBONITA provided a new perspective on the mechanisms of HIV-associated atherosclerosis. Lipid metabolism and cell migration pathways are induced by AS rather than by HIV infection. These pathways included AGE-RAGE and PI3K-AKT signaling in CD8+ T cells, and glucagon and cAMP signaling pathways in monocytes. Further analysis of other cell subpopulations suggests that the highly interconnected PI3K-AKT signaling pathway drives cell migratory state in response to dyslipidemia. scBONITA attractor analysis mapped cells to pathway-specific signaling states that correspond to distinct cellular states. Conclusions: Dynamic network modeling and pathway analysis with scBONITA indicates that dysregulated lipid signaling regulates cell migration into the vascular endothelium in AS+ PLWH. Attractor analysis with scBONITA facilitated pathway-based characterization of cellular states that are not apparent in gene expression analyses.

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Association of Viral Persistence and Atherosclerosis in Adults With Treated HIV Infection

Abstract: This cohort study assesses whether higher levels of viral persistence are associated with atherosclerosis as assessed by changes in carotid artery intima-media thickness over time in patients living with HIV.

Cited by 30 publications

References 69 publications

Investigating vascular diseases in people living with HIV by nuclear imaging

Investigating vascular diseases in people living with HIV by nuclear imaging

Suppression of Human Coronavirus 229E Infection in Lung Fibroblast Cells via RNA Interference

Executable models of immune signaling pathways in HIV-associated atherosclerosis

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