Human endogenous retroviruses and the inflammatory response: A vicious circle associated with health and illness

Rangel, Sara Coelho; Silva, Michelly Damasceno da; Silva, Amanda Lopes da; Santos, Juliana de Melo Batista dos; Neves, Lucas Melo; Pedrosa, Ana; Monteiro, Fernanda; Trettel, Caio dos Santos; Furtado, Guilherme Eustáquio; Barros, Marcelo Alves; Bacchi, André Luis Lacerda; Romano, Camila Malta; Nali, Luiz Henrique Da Silva

doi:10.3389/fimmu.2022.1057791

Cited by 20 publications

(21 citation statements)

References 166 publications

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“…As previously discussed, MS patients typically express high levels of MSRV and other HERVs belonging to the HERV-W family. Specifically, there is a 1.5- to 3-fold increase in HERV-W Env expression, which acts as a TLR4:CD14 agonist and induces the expression of various pro-inflammatory cytokines to promote neuroinflammation [ 130 ].…”

Section: Hervs In a Clinical Settingmentioning

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 In a Clinical Settingmentioning

confidence: 99%

Endogenous Retroviruses as Modulators of Innate Immunity

Russ

Iordanskiy

2023

Pathogens

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“…One of these is endogenous retroviruses (ERV). The activity of these diverse, abundant, and pervasive elements have been recognized as one of the drivers of innate immune responses to a microbe (41, 51, 76) . Our attention was drawn to ERVs by finding in the genome-wide RNA-seq of LPS-treated and control rats.…”

Section: Resultsmentioning

confidence: 99%

The white-footed deermouse, an infection-tolerant reservoir for several zoonotic agents, tempers interferon responses to endotoxin in comparison to the mouse and rat

Milovic

Duong

Barbour

2023

Preprint

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The white-footed deermouse Peromyscus leucopus, a long-lived rodent, is a key reservoir for agents of several zoonoses, including Lyme disease. While persistently infected, this deermouse is without apparent disability or diminished fitness. For a model for inflammation elicited by various pathogens, the endotoxin lipopolysaccharide (LPS) was used to compare genome-wide transcription in blood by P. leucopus, Mus musculus and Rattus norvegicus and adjusted for white cell concentrations. Deermice were distinguished from the mice and rats by LPS response profiles consistent with non-classical monocytes and alternatively-activated macrophages. LPS-treated P. leucopus, in contrast to mice and rats, also displayed little transcription of interferon-gamma and lower magnitude fold-changes in type 1 interferon-stimulated genes. This was associated with comparatively reduced transcription of endogenous retrovirus sequences and cytoplasmic pattern recognition receptors in the deermice. The results reveal a mechanism for infection tolerance in this species and perhaps other animal reservoirs for agents of human disease.

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“…Triggering agents for ME/CFS and FM, such as infections, stress, or trauma ( 15, 16 ), seem capable of disrupting the epigenetic mechanisms constraining HERV expression ( 40 ). Dysregulation of HERV has been proposed to contain more distinctive features than the host transcriptome itself in response to viral infections ( 41 ), and it is becoming detected in additional complex diseases ( 24 ), offering a new perspective to study their physiopathology.…”

Section: Discussionmentioning

confidence: 99%

HERV activation segregates ME/CFS from fibromyalgia and defines a novel nosological entity for patients fulfilling both clinical criteria

Giménez-Orenga,

Martín-Martínez,

Nathanson

et al. 2023

Preprint

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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and fibromyalgia (FM) are chronic diseases with poorly understood pathophysiology and diagnosis based on clinical assessment of unspecific symptoms. The recent post-COVID-19 condition, which shares similarities with ME/CFS and FM, has raised concerns about viral-induced transcriptome changes in post-viral syndromes. Viral infections, and other types of stress, are known to unleash human endogenous retroviruses (HERV) repression that if maintained could lead to symptom chronicity. This study evaluated this possibility for ME/CFS and FM on a selected cohort of female patients complying with diagnosis criteria for ME/CFS, FM, or both, and matched healthy controls (n=43). The results show specific HERV fingerprints for each disease, confirming biological differences between ME/CFS and FM. Unexpectedly, HERV profiles segregated patients that met both ME/CFS and FM clinical criteria from patients complying only with ME or FM criteria, while clearly differentiating patients from healthy subjects, supporting that the highly prevalent comorbidity condition must constitute a different nosological entity. Moreover, HERV profiles exposed significant quantitative differences within the ME/CFS group that correlated with differences in immune gene expression and patient symptomatology, supporting ME/CFS patient subtyping and confirming immunological disturbances in this disease. Pending issues include validation of HERV profiles as disease biomarkers of post-viral syndromes and understanding the role of HERV during infection and beyond.

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Human endogenous retroviruses and the inflammatory response: A vicious circle associated with health and illness

Cited by 20 publications

References 166 publications

Endogenous Retroviruses as Modulators of Innate Immunity

Endogenous Retroviruses as Modulators of Innate Immunity

The white-footed deermouse, an infection-tolerant reservoir for several zoonotic agents, tempers interferon responses to endotoxin in comparison to the mouse and rat

HERV activation segregates ME/CFS from fibromyalgia and defines a novel nosological entity for patients fulfilling both clinical criteria

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