Molecular mechanisms of human herpes viruses inferring with host immune surveillance

Jasinski‐Bergner, Simon; Mandelboim, Ofer; Seliger, Barbara

doi:10.1136/jitc-2020-000841

Cited by 20 publications

(15 citation statements)

References 135 publications

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“…HSV-1 and EBV herpesviruses were most present, and EBV coinfection was evidenced in about 30% of COVID-19 patients compared to only 5% of controls. In this regard, the HOM dysbiosis may have facilitated the activation/reactivation of oral viruses, and in turn, the high presence of herpesviruses infection/reactivation may further impair proper immune control ( Jasinski-Bergner et al, 2020 ), thus potentially contributing to worse efficiency of the immune response against SARS-CoV-2. Consistent with this, EBV infection was detected in COVID-19 patients, associated with increased risk of severe COVID-19 symptoms and fatal outcome ( Roncati et al, 2020 ; Chen et al, 2021 ), and correlated increased levels of IL-6 ( Lehner et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Oral Microbiome Dysbiosis Is Associated With Symptoms Severity and Local Immune/Inflammatory Response in COVID-19 Patients: A Cross-Sectional Study

et al. 2021

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The human oral microbiome (HOM) is the second largest microbial community after the gut and can impact the onset and progression of several localized and systemic diseases, including those of viral origin, especially for viruses entering the body via the oropharynx. However, this important aspect has not been clarified for the new pandemic human coronavirus SARS-CoV-2, causing COVID-19 disease, despite it being one of the many respiratory viruses having the oropharynx as the primary site of replication. In particular, no data are available about the non-bacterial components of the HOM (fungi, viruses), which instead has been shown to be crucial for other diseases. Consistent with this, this study aimed to define the HOM in COVID-19 patients, to evidence any association between its profile and the clinical disease. Seventy-five oral rinse samples were analyzed by Whole Genome Sequencing (WGS) to simultaneously identify oral bacteria, fungi, and viruses. To correlate the HOM profile with local virus replication, the SARS-CoV-2 amount in the oral cavity was quantified by digital droplet PCR. Moreover, local inflammation and secretory immune response were also assessed, respectively by measuring the local release of pro-inflammatory cytokines (L-6, IL-17, TNFα, and GM-CSF) and the production of secretory immunoglobulins A (sIgA). The results showed the presence of oral dysbiosis in COVID-19 patients compared to matched controls, with significantly decreased alpha-diversity value and lower species richness in COVID-19 subjects. Notably, oral dysbiosis correlated with symptom severity (p = 0.006), and increased local inflammation (p < 0.01). In parallel, a decreased mucosal sIgA response was observed in more severely symptomatic patients (p = 0.02), suggesting that local immune response is important in the early control of virus infection and that its correct development is influenced by the HOM profile. In conclusion, the data presented here suggest that the HOM profile may be important in defining the individual susceptibility to SARS-CoV-2 infection, facilitating inflammation and virus replication, or rather, inducing a protective IgA response. Although it is not possible to determine whether the alteration in the microbial community is the cause or effect of the SARS-CoV-2 replication, these parameters may be considered as markers for personalized therapy and vaccine development.

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Section: Discussionmentioning

confidence: 99%

Oral Microbiome Dysbiosis Is Associated With Symptoms Severity and Local Immune/Inflammatory Response in COVID-19 Patients: A Cross-Sectional Study

et al. 2021

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“…It has been well established that cells of the innate and adaptive immune system are able to recognize and eliminate cancer cells. However, the processes of malignant and/or viral transformation, as well as increased growth, are associated with strategies of tumor cells to escape immune surveillance [223] by evading the immune surveillance and/or by suppressing the hosts' immune system mediated by shaping the TME and dampening the effector function [224,225]. Indeed, tumor cells can convert immune cells to a tolerogenic and dysfunctional state due to cell-cell interactions, soluble mediators and physical factors in the TME.…”

Section: Immune Escape Of Ebv-infected Cellsmentioning

confidence: 99%

Epstein–Barr Virus—Associated Malignancies and Immune Escape: The Role of the Tumor Microenvironment and Tumor Cell Evasion Strategies

Bauer

Jasinski‐Bergner

Mandelboim

et al. 2021

Cancers

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The detailed mechanisms of Epstein–Barr virus (EBV) infection in the initiation and progression of EBV-associated malignancies are not yet completely understood. During the last years, new insights into the mechanisms of malignant transformation of EBV-infected cells including somatic mutations and epigenetic modifications, their impact on the microenvironment and resulting unique immune signatures related to immune system functional status and immune escape strategies have been reported. In this context, there exists increasing evidence that EBV-infected tumor cells can influence the tumor microenvironment to their own benefit by establishing an immune-suppressive surrounding. The identified mechanisms include EBV gene integration and latent expression of EBV-infection-triggered cytokines by tumor and/or bystander cells, e.g., cancer-associated fibroblasts with effects on the composition and spatial distribution of the immune cell subpopulations next to the infected cells, stroma constituents and extracellular vesicles. This review summarizes (i) the typical stages of the viral life cycle and EBV-associated transformation, (ii) strategies to detect EBV genome and activity and to differentiate various latency types, (iii) the role of the tumor microenvironment in EBV-associated malignancies, (iv) the different immune escape mechanisms and (v) their clinical relevance. This gained information will enhance the development of therapies against EBV-mediated diseases to improve patient outcome.

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“…HLA antigens are critical for both the innate and adaptive immune systems as they bind to T cell receptors to present HLA-restricted peptides to T cells and interact with NK cell receptors to modulate the functions of innate immune components, such as NK cells ( 43 ). Downregulation of the expression of the classical HLA class I antigens (HLA-A, -B, and -C) and HLA class II antigens (DP, DQ, and DR) is one of the most effective strategies for perpetuating viral infections, as it allows virus-infected cells to escape from the host immune attack led by virus-specific CD8+ T cells and blunt CD4+ T cells, which help B cells to produce virus-specific antibodies ( 44 ). The aberrant upregulation of the immune tolerant HLA-G expression is more common than the downregulation of the HLA-I and -II antigens during many infections, providing virus-infected cells a strategy to protect themselves from NK cell cytolysis ( 45 , 46 ).…”

Section: Induction Of Hla-g Expression In Infectious Diseasesmentioning

confidence: 99%

Perspective of HLA-G Induced Immunosuppression in SARS-CoV-2 Infection

Lin

Yan

2021

Front. Immunol.

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COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has threatened public health worldwide. Host antiviral immune responses are essential for viral clearance and disease control, however, remarkably decreased immune cell numbers and exhaustion of host cellular immune responses are commonly observed in patients with COVID-19. This is of concern as it is closely associated with disease severity and poor outcomes. Human leukocyte antigen-G (HLA-G) is a ligand for multiple immune inhibitory receptors, whose expression can be upregulated by viral infections. HLA-G/receptor signalling, such as engagement with immunoglobulin-like transcript 2 (ILT-2) or ILT-4, not only inhibit T and natural killer (NK) cell immune responses, dendritic cell (DC) maturation, and B cell antibody production. It also induces regulatory cells such as myeloid-derived suppressive cells (MDSCs), or M2 type macrophages. Moreover, HLA-G interaction with CD8 and killer inhibitory receptor (KIR) 2DL4 can provoke T cell apoptosis and NK cell senescence. In this context, HLA-G can induce profound immune suppression, which favours the escape of SARS-CoV-2 from immune attack. Although detailed knowledge on the clinical relevance of HLA-G in SARS-CoV-2 infection is limited, we herein review the immunopathological aspects of HLA-G/receptor signalling in SARS-CoV-2 infection, which could provide a better understanding of COVID-19 disease progression and identify potential immunointerventions to counteract SARS-CoV-2 infection.

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Molecular mechanisms of human herpes viruses inferring with host immune surveillance

Cited by 20 publications

References 135 publications

Oral Microbiome Dysbiosis Is Associated With Symptoms Severity and Local Immune/Inflammatory Response in COVID-19 Patients: A Cross-Sectional Study

Oral Microbiome Dysbiosis Is Associated With Symptoms Severity and Local Immune/Inflammatory Response in COVID-19 Patients: A Cross-Sectional Study

Epstein–Barr Virus—Associated Malignancies and Immune Escape: The Role of the Tumor Microenvironment and Tumor Cell Evasion Strategies

Perspective of HLA-G Induced Immunosuppression in SARS-CoV-2 Infection

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