scholarly journals Systems Biology to Understand and Regulate Human Retroviral Proinflammatory Response

2021 ◽  
Vol 12 ◽  
Author(s):  
Mohamed Helmy ◽  
Kumar Selvarajoo
Keyword(s):  
Immune Response ◽  
Systems Biology ◽  
Transposable Elements ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Endogenous Retroviruses ◽  
Therapeutic Approaches ◽  
Genome Sequences ◽  
Proinflammatory Response ◽  
Novel Therapeutic

The majority of human genome are non-coding genes. Recent research have revealed that about half of these genome sequences make up of transposable elements (TEs). A branch of these belong to the endogenous retroviruses (ERVs), which are germline viral infection that occurred over millions of years ago. They are generally harmless as evolutionary mutations have made them unable to produce viral agents and are mostly epigenetically silenced. Nevertheless, ERVs are able to express by still unknown mechanisms and recent evidences have shown links between ERVs and major proinflammatory diseases and cancers. The major challenge is to elucidate a detailed mechanistic understanding between them, so that novel therapeutic approaches can be explored. Here, we provide a brief overview of TEs, human ERVs and their links to microbiome, innate immune response, proinflammatory diseases and cancer. Finally, we recommend the employment of systems biology approaches for future HERV research.

scholarly journals Extracellular Vesicles Released by Colorectal Cancer Cell Lines Modulate Innate Immune Response in Zebrafish Model: The Possible Role of Human Endogenous Retroviruses

2019 ◽  
Vol 20 (15) ◽  
pp. 3669 ◽  
Author(s):  
Luca Ferrari ◽  
Marco Cafora ◽  
Federica Rota ◽  
Mirjam Hoxha ◽  
Simona Iodice ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Cell Lines ◽  
Cancer Cell ◽  
Innate Immune Response ◽  
Colorectal Adenocarcinoma ◽  
Innate Immune ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retroviruses ◽  
Colorectal Cancer Cell Lines

Extracellular vesicles (EVs) are important components of the metastatic niche and are crucial in infiltration, metastasis, and immune tolerance processes during tumorigenesis. We hypothesized that human endogenous retroviruses (HERV) positive EVs derived from tumor cellsmay have a role in modulating the innate immune response. The study was conducted in two different colorectal cancer cell lines, representing different stages of cancer development: Caco-2, derived from a non-metastatic colorectal adenocarcinoma, and SK-CO-1, derived from metastatic colorectal adenocarcinoma (ascites). Both cell lines were treated with decitabine to induce global hypomethylation and to reactivate HERV expression. EVs were quantified by nanoparticle tracking analysis, and HERV-positive EV concentrations were measured by flow cytometry. The effect of EVs isolated from both untreated and decitabine-treated cells on the innate immune response was evaluated by injecting them in zebrafish embryos and then assessing Interleukin 1β (IL1-β), Interleukin 10 (IL-10), and the myeloperoxidase (mpx) expression levels by real-time qPCR. Interestingly, HERV-K positive EVs concentrations were significantly associated with a reduced expression of IL1-β and mpx, supporting our hypothesis that HERV-positive EVs may act as immunomodulators in tumor progression. The obtained results open new perspectives about the modulation of the immune response in cancer therapy.

scholarly journals Re-evaluation of hepatitis B virus clinical phases by systems biology identifies unappreciated roles for the innate immune response and B cells

Hepatology ◽  
2015 ◽  
Vol 62 (1) ◽  
pp. 87-100 ◽  
Author(s):  
Thomas Vanwolleghem ◽  
Jun Hou ◽  
Gertine van Oord ◽  
Arno C. Andeweg ◽  
A.D.M.E. Osterhaus ◽  
...  
Keyword(s):  
Immune Response ◽  
Systems Biology ◽  
Hepatitis B Virus ◽  
B Cells ◽  
Hepatitis B ◽  
Innate Immune Response ◽  
Innate Immune ◽  
B Virus

TRANSCRIPTIONAL ANALYSIS OF THE INNATE IMMUNE RESPONSE USING SYSTEMS BIOLOGY METHODOLOGY

Shock ◽  
2006 ◽  
Vol 25 (Supplement 1) ◽  
pp. 77
Author(s):  
Y. Gusev ◽  
M. Lerner ◽  
J. Hanas ◽  
S. Do ◽  
S. Lightfoot ◽  
...  
Keyword(s):  
Immune Response ◽  
Systems Biology ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Transcriptional Analysis

scholarly journals Human Endogenous Retroviruses (HERVs): Shaping the Innate Immune Response in Cancers

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 610 ◽  
Author(s):  
Vincent Alcazer ◽  
Paola Bonaventura ◽  
Stephane Depil
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Endogenous Retroviruses ◽  
Interferon Response ◽  
Human Endogenous Retroviruses ◽  
Dna Production ◽  
Potential Impact ◽  
Multiple Conditions

Human Endogenous Retroviruses (HERVs) are accounting for 8% of the human genome. These sequences are remnants from ancient germline infections by exogenous retroviruses. After million years of evolution and multiple integrations, HERVs have acquired many damages rendering them defective. At steady state, HERVs are mostly localized in the heterochromatin and silenced by methylation. Multiple conditions have been described to induce their reactivation, including auto-immune diseases and cancers. HERVs re-expression leads to RNA (simple and double-stranded) and DNA production (by reverse transcription), modulating the innate immune response. Some studies also argue for a role of HERVs in shaping the evolution of innate immunity, notably in the development of the interferon response. However, their exact role in the innate immune response, particularly in cancer, remains to be defined. In this review, we see how HERVs could be key-players in mounting an antitumor immune response. After a brief introduction on HERVs characteristics and biology, we review the different mechanisms by which HERVs can interact with the immune system, with a focus on the innate response. We then discuss the potential impact of HERVs expression on the innate immune response in cancer.

scholarly journals Systems-Biology Approaches to Discover Anti-Viral Effectors of the Human Innate Immune Response

Viruses ◽  
2011 ◽  
Vol 3 (7) ◽  
pp. 1112-1130 ◽  
Author(s):  
Carsten Münk ◽  
Andreas F.R. Sommer ◽  
Renate König
Keyword(s):  
Immune Response ◽  
Systems Biology ◽  
Innate Immune Response ◽  
Innate Immune

scholarly journals Bacterial Pathogens Hijack the Innate Immune Response by Activation of the Reverse Transsulfuration Pathway

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Alain P. Gobert ◽  
Yvonne L. Latour ◽  
Mohammad Asim ◽  
Jordan L. Finley ◽  
Thomas G. Verriere ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Metabolic Pathway ◽  
Pathogenic Bacteria ◽  
Immune Escape ◽  
Bacterial Pathogens ◽  
Innate Immune ◽  
Polyamine Metabolism ◽  
Proinflammatory Response ◽  
Transsulfuration Pathway

ABSTRACT The reverse transsulfuration pathway is the major route for the metabolism of sulfur-containing amino acids. The role of this metabolic pathway in macrophage response and function is unknown. We show that the enzyme cystathionine γ-lyase (CTH) is induced in macrophages infected with pathogenic bacteria through signaling involving phosphatidylinositol 3-kinase (PI3K)/MTOR and the transcription factor SP1. This results in the synthesis of cystathionine, which facilitates the survival of pathogens within myeloid cells. Our data demonstrate that the expression of CTH leads to defective macrophage activation by (i) dysregulation of polyamine metabolism by depletion of S-adenosylmethionine, resulting in immunosuppressive putrescine accumulation and inhibition of spermidine and spermine synthesis, and (ii) increased histone H3K9, H3K27, and H3K36 di/trimethylation, which is associated with gene expression silencing. Thus, CTH is a pivotal enzyme of the innate immune response that disrupts host defense. The induction of the reverse transsulfuration pathway by bacterial pathogens can be considered an unrecognized mechanism for immune escape. IMPORTANCE Macrophages are professional immune cells that ingest and kill microbes. In this study, we show that different pathogenic bacteria induce the expression of cystathionine γ-lyase (CTH) in macrophages. This enzyme is involved in a metabolic pathway called the reverse transsulfuration pathway, which leads to the production of numerous metabolites, including cystathionine. Phagocytized bacteria use cystathionine to better survive in macrophages. In addition, the induction of CTH results in dysregulation of the metabolism of polyamines, which in turn dampens the proinflammatory response of macrophages. In conclusion, pathogenic bacteria can evade the host immune response by inducing CTH in macrophages.

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