Viral Mimicry Response Is Associated With Clinical Outcome in Pleural Mesothelioma

Sun, Suna; Qi, Weihong; Rehrauer, Hubert; Ronner, Manuel; Hariharan, Ananya; Wipplinger, Martin; Meiller, Clément; Stahel, Rolf A.; Früh, Martin; Cerciello, Ferdinando; Fonteneau, Jean‐François; Jean, Didier; Felley‐Bosco, Emanuela

doi:10.1016/j.jtocrr.2022.100430

Cited by 3 publications

(11 citation statements)

References 67 publications

(117 reference statements)

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“…While not all of these receptor classes have demonstrated the ability to recognize HERV-derived products, the viral-like nature of particular HERV-derived DNA, RNA, and proteins allows them to be recognized by and stimulate various PRRs to induce an innate immune response, similar to that of exogenous viruses. As a result, the effects of aberrant HERV upregulation are said to mimic the anti-viral state that is induced following viral infection, leading to coinage of the term “ viral mimicry ” when discussing the implications of HERV re-activation on the innate immune response [ 37 , 73 , 74 ]. Specific PRRs involved in the activation of innate immunity following HERV upregulation and their signaling pathways are depicted in Figure 4 and summarized in Table 1 .…”

Section: Hervs As Activators Of the Innate Immune Responsementioning

confidence: 99%

Endogenous Retroviruses as Modulators of Innate Immunity

Russ

Iordanskiy

2023

Pathogens

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Endogenous retroviruses (ERVs), or LTR retrotransposons, are a class of transposable elements that are highly represented in mammalian genomes. Human ERVs (HERVs) make up roughly 8.3% of the genome and over the course of evolution, HERV elements underwent positive selection and accrued mutations that rendered them non-infectious; thereby, the genome could co-opt them into constructive roles with important biological functions. In the past two decades, with the help of advances in sequencing technology, ERVs are increasingly considered to be important components of the innate immune response. While typically silenced, expression of HERVs can be induced in response to traumatic, toxic, or infection-related stress, leading to a buildup of viral transcripts and under certain circumstances, proteins, including functionally active reverse transcriptase and viral envelopes. The biological activity of HERVs in the context of the innate immune response can be based on the functional effect of four major viral components: (1) HERV LTRs, (2) HERV-derived RNAs, (3) HERV-derived RNA:DNA duplexes and cDNA, and 4) HERV-derived proteins and ribonucleoprotein complexes. In this review, we will discuss the implications of HERVs in all four contexts in relation to innate immunity and their association with various pathological disease states.

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Section: Hervs As Activators Of the Innate Immune Responsementioning

confidence: 99%

Endogenous Retroviruses as Modulators of Innate Immunity

Russ

Iordanskiy

2023

Pathogens

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“…In this review, we focus on the expression of transposable elements (TE), in particular endogenous retroviruses in mesothelioma. Indeed, although they are frequently not investigated in transcriptomics studies because of their repetitive nature, we observed that their expression increases upon mesothelioma development [9] and is associated with better overall survival [10].…”

Section: Introduction: Why It Is Important To Explore Expressed Genom...mentioning

confidence: 72%

“…In human mesothelioma, we observed that the ERV1 family, which belongs to ERV Class I, has the highest number of upregulated or downregulated loci in ERVs when compared to mesothelial cells [10].…”

Section: Endogenous Retroviruses Are the Te With Highest Variation In...mentioning

confidence: 84%

“…There are more than 1000 HERV-K loci in the human genome; however, most of them are "solo-LTRs" [41]. HERV-K family members are less enriched in mesothelioma when compared to mesothelial precursors [10]. ERVmap-k48, also called HERV-K15 [42] had the same expression levels in mesothelioma and mesothelial cells [10].…”

Section: Endogenous Retroviruses Are the Te With Highest Variation In...mentioning

confidence: 99%

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Exploring the Expression of the «Dark Matter» of the Genome in Mesothelioma for Potentially Predictive Biomarkers for Prognosis and Immunotherapy

Felley‐Bosco

2023

Cancers

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Recent high-throughput RNA sequencing technologies have confirmed that a large part of the non-coding genome is transcribed. The priority for further investigations is nevertheless generally given in cancer to coding sequences, due to the obvious interest of finding therapeutic targets. In addition, several RNA-sequencing pipelines eliminate repetitive sequences, which are difficult to analyze. In this review, we shall focus on endogenous retroviruses. These sequences are remnants of ancestral germline infections by exogenous retroviruses. These sequences represent 8% of human genome, meaning four-fold the fraction of the genome encoding for proteins. These sequences are generally mostly repressed in normal adult tissues, but pathological conditions lead to their de-repression. Specific mesothelioma-associated endogenous retrovirus expression and their association to clinical outcome is discussed.

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“…Mesothelioma was originally described in 1931, but it wasn not until 1960 that South African epidemiological research linked it to asbestos exposure ( 20 ). It is now known that mesothelioma in men is caused by occupational asbestos exposure in 85 percent of cases, while only 10 percent of individuals with asbestos exposure develop mesothelioma ( 21 ). The possibility of acquiring lung cancer increases tenfold to one hundredfold when asbestos exposure is combined with cigarette smoking.…”

Section: Pathogenesismentioning

confidence: 99%

Malignant mesothelioma tumours: molecular pathogenesis, diagnosis, and therapies accompanying clinical studies

et al. 2023

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The pathetic malignant mesothelioma (MM) is a extremely uncommon and confrontational tumor that evolves in the mesothelium layer of the pleural cavities (inner lining- visceral pleura and outer lining- parietal pleura), peritoneum, pericardium, and tunica vaginalis and is highly resistant to standard treatments. In mesothelioma, the predominant pattern of lesions is a loss of genes that limit tumour growth. Despite the worldwide ban on the manufacture and supply of asbestos, the prevalence of mesothelioma continues to increase. Mesothelioma presents and behaves in a variety of ways, making diagnosis challenging. Most treatments available today for MM are ineffective, and the median life expectancy is between 10 and 12 months. However, in recent years, considerable progress has already been made in understanding the genetics and molecular pathophysiology of mesothelioma by addressing hippo signaling pathway. The development and progression of MM are related to many important genetic alterations. This is related to NF2 and/or LATS2 mutations that activate the transcriptional coactivator YAP. The X-rays, CT scans, MRIs, and PET scans are used to diagnose the MM. The MM are treated with surgery, chemotherapy, first-line combination chemotherapy, second-line treatment, radiation therapy, adoptive T-cell treatment, targeted therapy, and cancer vaccines. Recent clinical trials investigating the function of surgery have led to the development of innovative approaches to the treatment of associated pleural effusions as well as the introduction of targeted medications. An interdisciplinary collaborative approach is needed for the effective care of persons who have mesothelioma because of the rising intricacy of mesothelioma treatment. This article highlights the key findings in the molecular pathogenesis of mesothelioma, diagnosis with special emphasis on the management of mesothelioma.

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Viral Mimicry Response Is Associated With Clinical Outcome in Pleural Mesothelioma

Cited by 3 publications

References 67 publications

Endogenous Retroviruses as Modulators of Innate Immunity

Endogenous Retroviruses as Modulators of Innate Immunity

Exploring the Expression of the «Dark Matter» of the Genome in Mesothelioma for Potentially Predictive Biomarkers for Prognosis and Immunotherapy

Malignant mesothelioma tumours: molecular pathogenesis, diagnosis, and therapies accompanying clinical studies

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