Kaposi’s sarcoma-associated herpesvirus infection of neurons in HIV positive patients

Tso, For Yue; Sawyer, Ashley; Kwon, Eun Hee; Mudenda, Victor; Langford, Dianne; Zhou, You; West, John T.; Wood, Charles

doi:10.1093/infdis/jiw545

Cited by 20 publications

(19 citation statements)

References 40 publications

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“…Adjacent 6 µm-thick sections of paraffin-embedded KS tissues were used for IHC, as previously described [55]. Mouse anti-LANA antibody clone NCL-L-HHV8-LNA (1:100) (Leica Biosystems, Newcastle, UK), antihuman CD8 clone C8/144B (1:100) (Agilent, Santa Clara, CA) or anti-human CD8 clone 4B11 (1:40) (GeneTex, Irvine, CA) were used as primary antibodies.…”

Section: Immunohistochemistry (Ihc) and Cell Quantificationmentioning

confidence: 99%

Lack of CD8+ T-cell co-localization with Kaposi’s sarcoma-associated herpesvirus infected cells in Kaposi’s sarcoma tumors

et al. 2020

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Despite the close association between Kaposi's sarcoma (KS) and immune dysfunction, it remains unclear whether tumor infiltrating immune cells (TIIC), by their absence, presence, or dysfunction, are mechanistically correlated with KS pathogenesis. Therefore, their potential capacity to serve as prognostic biomarkers of KS disease progression or control is unclear. Because epidemic-KS (EpKS) occurs with HIV-1 co-infection, it is particularly important to compare TIIC between EpKS and HIV-negative African endemic-KS (EnKS) to dissect the roles of HIV-1 and Kaposi Sarcoma-associated herpesvirus (KSHV) in KS pathogenesis. This cross-sectional study of 13 advanced KS (4 EnKS, 9 EpKS) patients and 3 healthy controls utilized single-color immunohistochemistry and dual-color immunofluorescence assays to characterize and quantify KSHV infected cells in relation to various TIIC in KS biopsies. Analysis of variance (ANOVA) and Mann-Whitney tests were used to assess differences between groups where P-values < 0.05 were considered significant. The abundance of KSHV infected cells was heterogeneous in KS biopsies. Despite the presence of T-cell chemoattractant chemokine CxCL-9 in biopsies, CD8 + T-cells were sparsely distributed in regions with evident KSHV infected cells but were readily detectable in regions devoid of KSHV infected cells (P < 0.0001). CD68 + (M1) macrophages were evenly and diffusely distributed in KS biopsies, whereas, the majority of CD163 + (M2) macrophages were localized in regions devoid of KSHV infected cells (P < 0.0001). Overall, the poor immune cell infiltration or co-localization in KS biopsies independent of HIV-1 co-infection suggests a fundamental tumor immune evasion mechanism that warrants further investigation.

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Section: Immunohistochemistry (Ihc) and Cell Quantificationmentioning

confidence: 99%

Lack of CD8+ T-cell co-localization with Kaposi’s sarcoma-associated herpesvirus infected cells in Kaposi’s sarcoma tumors

et al. 2020

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“…Virus infections are the most frequent reason for encephalitis. A variety of viruses affect the CNS and induce encephalitis, including flaviviruses such as Dengue [ 275 , 276 ], hepatitis C [ 277 ], Japanese encephalitis [ 278 , 279 ], West Nile [ 44 ] and Zika [ 280 – 282 ], as well as herpes viruses such as herpes simplex [ 283 ], varicella Zoster [ 284 ] and Kaposi’s sarcoma associated herpes virus [ 285 ], as well as HIV [ 286 , 287 ]. All the viruses mentioned above may infect microglia [ 276 – 278 , 280 , 281 , 288 ], whereas flaviviruses and herpes viruses, but not HIV [ 289 ], may also infect neurons and/or astroglia.…”

Section: Introductionmentioning

confidence: 99%

Microglia at center stage: a comprehensive review about the versatile and unique residential macrophages of the central nervous system

et al. 2017

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Microglia cells are the unique residential macrophages of the central nervous system (CNS). They have a special origin, as they derive from the embryonic yolk sac and enter the developing CNS at a very early stage. They play an important role during CNS development and adult homeostasis. They have a major contribution to adult neurogenesis and neuroinflammation. Thus, they participate in the pathogenesis of neurodegenerative diseases and contribute to aging. They play an important role in sustaining and breaking the blood-brain barrier. As innate immune cells, they contribute substantially to the immune response against infectious agents affecting the CNS. They play also a major role in the growth of tumours of the CNS. Microglia are consequently the key cell population linking the nervous and the immune system. This review covers all different aspects of microglia biology and pathology in a comprehensive way.

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“…KSHV is in the same family as Epstein-Barr virus (EBV), the virus that causes infectious mononucleosis (mono) and is linked to several types of cancer [49]. Recent studies have found a strong link between the activity of specific viral species (three herpesviruses: HSV1 HHV-6 and HHV-7), with molecular, genetic, clinical, and neuropathological aspects of AD [50,51].…”

Section: Discussionmentioning

confidence: 99%

PathWalks: Identifying pathway communities using a disease-related map of integrated information

Karatzas¹,

Zachariou

Bourdakou

et al. 2020

Preprint

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AbstractUnderstanding disease underlying biological mechanisms and respective interactions remains an elusive, time consuming and costly task. The realization of computational methodologies that can propose pathway/mechanism communities and reveal respective relationships can be of great value as it can help expedite the process of identifying how perturbations in a single pathway can affect other pathways.Random walks is a stochastic approach that can be used for both efficient discovery of strong connections and identification of communities formed in networks. The approach has grown in popularity as it efficiently exposes key network components and reveals strong interactions among genes, proteins, metabolites, pathways and drugs. Using random walks in biology, we need to overcome two key challenges: 1) construct disease-specific biological networks by integrating information from available data sources as they become available, and 2) provide guidance to the walker so as it can follow plausible trajectories that comply with inherent biological constraints.In this work, we present a methodology called PathWalks, where a random walker crosses a pathway-to-pathway network under the guidance of a disease-related map. The latter is a gene network that we construct by integrating multi-source information regarding a specific disease. The most frequent trajectories highlight communities of pathways that are expected to be strongly related to the disease under study. We present maps for Alzheimer’s Disease and Idiopathic Pulmonary Fibrosis and we use them as case-studies for identifying pathway communities through the application of PathWalks.In the case of Alzheimer’s Disease, the most visited pathways are the “Alzheimer’s disease” and the “Calcium signaling” pathways which have indeed the strongest association with Alzheimer’s Disease. Interestingly however, in the top-20 visited pathways we identify the “Kaposi sarcoma-associated herpesvirus infection” (HHV-8) and the “Human papillomavirus infection” (HPV) pathways suggesting that viruses may be involved in the development and progression of Alzheimer’s. Similarly, most of the highlighted pathways in Idiopathic Pulmonary Fibrosis are backed by the bibliography. We establish that “MAPK signaling” and “Cytokine-cytokine receptor interaction” pathways are the most visited. However, the “NOD receptor signaling” pathway is also in the top-40 edges. In Idiopathic Pulmonary Fibrosis samples, increased NOD receptor signaling has been associated with augmented concentrations of certain strains of Streptococcus. Additional experimental evidence is required however to further explore and ascertain the above indications.

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Kaposi’s sarcoma-associated herpesvirus infection of neurons in HIV positive patients

Abstract: Our study showed that KSHV infects human CNS-resident cells, primarily neurons, in HIV-positive Zambian individuals.

Cited by 20 publications

References 40 publications

Lack of CD8+ T-cell co-localization with Kaposi’s sarcoma-associated herpesvirus infected cells in Kaposi’s sarcoma tumors

Lack of CD8+ T-cell co-localization with Kaposi’s sarcoma-associated herpesvirus infected cells in Kaposi’s sarcoma tumors

Microglia at center stage: a comprehensive review about the versatile and unique residential macrophages of the central nervous system

PathWalks: Identifying pathway communities using a disease-related map of integrated information

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