Endogenous Retroviruses Walk a Fine Line between Priming and Silencing

Cullen, Harrison B.; Schorn, Andrea

doi:10.3390/v12080792

Cited by 16 publications

(10 citation statements)

References 154 publications

(245 reference statements)

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“…Over 3,000 of human endogenous retroviruses (HERVs) are integrated into the host genome, comprising about 8% of human DNA [38]. Accordingly, the HERVs play important and diverse roles in human biology that cannot be discussed in this brief review in any detail (for recent reviews, see [39][40][41][42]). Most of the HERVs appear to descend from ancient integration events so that the virus genes are disrupted and rearranged.…”

Section: Kingdom Pararnaviramentioning

confidence: 99%

The healthy human virome: from virus–host symbiosis to disease

Koonin

Dolja

Krupovìč

2021

Current Opinion in Virology

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Viruses are ubiquitous, essential components of any ecosystem, and of multicellular organism holobionts. Numerous viruses cause acute infection, killing the host or being cleared by immune system. In many other cases, viruses coexist with the host as symbionts, either temporarily or for the duration of the host's life. Apparently, virus-host relationships span the entire range from aggressive parasitism to mutualism. Here we attempt to delineate the healthy human virome, that is, the entirety of viruses that are present in a healthy human body. The bulk of the healthy virome consists of bacteriophages infecting bacteria in the intestine and other locations. However, a variety of viruses, such as anelloviruses and herpesviruses, and the numerous endogenous retroviruses, persist by replicating in human cells, and these are our primary focus. Crucially, the boundary between symbiotic and pathogenic viruses is fluid such that members of the healthy virome can become pathogens under changing conditions.

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Section: Kingdom Pararnaviramentioning

confidence: 99%

The healthy human virome: from virus–host symbiosis to disease

Koonin

Dolja

Krupovìč

2021

Current Opinion in Virology

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“…Where the majoritycontain an additional T nucleotide ( Figure 2 ). In a murine retrovirus, 2–3 mutations in PBS lys1,2 , including a single nt insertion, have been shown to be tolerated in replication while conveying escape from tRNA fragment (tRF) repression [ 38 ]. HIV-1 can likewise allow 1–2 nt insertions in its PBS [ 39 ].…”

Section: Resultsmentioning

confidence: 99%

Analysis of Simian Endogenous Retrovirus (SERV) Full-Length Proviruses in Old World Monkey Genomes

Kuyl

2022

Genes

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Simian endogenous retrovirus, SERV, is a successful germ line invader restricted to Old World monkey (OWM) species. (1) Background: The availability of high-quality primate genomes warrants a study of the characteristics, evolution, and distribution of SERV proviruses. (2) Methods: Cercopithecinae OWM genomes from public databases were queried for the presence of full-length SERV proviruses. A dataset of 81 Cer-SERV genomes was generated and analyzed. (3) Results: Full-length Cer-SERV proviruses were mainly found in terrestrial OWM, and less so in arboreal, forest- dwelling monkeys. Phylogenetic analysis confirmed the existence of two genotypes, Cer-SERV-1 and Cer-SERV-2, with Cer-SERV-1 showing evidence of recent germ-line expansions. Long Terminal Repeat (LTR) variation indicated that most proviruses were of a similar age and were estimated to be between <0.3 and 10 million years old. Integrations shared between species were relatively rare. Sequence analysis further showed extensive CpG methylation-associated mutations, variable Primer Binding Site (PBS) use with Cer-SERV-1 using PBSlys3 and Cer-SERV-2 using PBSlys1,2, and the recent gain of LTR motifs for transcription factors active during embryogenesis in Cer-SERV-1. (4) Conclusions: sequence analysis of 81 SERV proviruses from Cercopithecinae OWM genomes provides evidence for the adaptation of this retrovirus to germ line reproduction.

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“…Theoretically, integrated ERVs sequences still retain a residual expression capacity and could produce a variety of coding or non-coding RNAs, cytosolic DNAs, and defective proviruses proteins [ 40 ]. The LTRs play a crucial role in regulating viral genes' transcription, including promoters, enhancers, and polyadenylation signals during ERVs reverse transcription [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

Activation of endogenous retrovirus triggers microglial immuno-inflammation and contributes to negative emotional behaviors in mice with chronic stress

Bao

Yan

Huang

et al. 2023

J Neuroinflammation

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Background The “missing” link of complex and multifaceted interplay among endogenous retroviruses (ERVs) transcription, chronic immuno-inflammation, and the development of psychiatric disorders is still far from being completely clarified. The present study was aimed to investigate the mechanism of protective role of inhibiting ERVs on reversing microglial immuno-inflammation in basolateral amygdala (BLA) in chronic stress-induced negative emotional behaviors in mice. Methods Male C57BL/6 mice were exposed to chronic unpredictable mild stress (CUMS) for 6 w. Negative emotional behaviors were comprehensively investigated to identify the susceptible mice. Microglial morphology, ERVs transcription, intrinsic nucleic acids sensing response, and immuno-inflammation in BLA were assessed. Results Mice with chronic stress were presented as obviously depressive- and anxiety-like behaviors, and accompanied with significant microglial morphological activation, murine ERVs genes MuERV-L, MusD, and IAP transcription, cGAS–IFI16–STING pathway activation, NF-κB signaling pathway priming, as well as NLRP3 inflammasome activation in BLA. Antiretroviral therapy, pharmacological inhibition of reverse transcriptases, as well as knocking-down the ERVs transcriptional regulation gene p53 significantly inhibited microglial ERVs transcription and immuno-inflammation in BLA, as well as improved the chronic stress-induced negative emotional behaviors. Conclusions Our results provided an innovative therapeutic approach that targeting ERVs-associated microglial immuno-inflammation may be beneficial to the patients with psychotic disorders.

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Endogenous Retroviruses Walk a Fine Line between Priming and Silencing

Cited by 16 publications

References 154 publications

The healthy human virome: from virus–host symbiosis to disease

The healthy human virome: from virus–host symbiosis to disease

Analysis of Simian Endogenous Retrovirus (SERV) Full-Length Proviruses in Old World Monkey Genomes

Activation of endogenous retrovirus triggers microglial immuno-inflammation and contributes to negative emotional behaviors in mice with chronic stress

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