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At least 19 recordsLinked to original sources
PubMed1978

Nucleotide sequence relationship between intracisternal type A particles of Mus musculus and an endogenous retrovirus (M432) of Mus cervicolor.

Intracisternal type A particles are retrovirus-like structures found in embryonic cells and many tumors of Mus musculus but having no clear relationship with other retroviruses of this mouse species. We have observed a partial nucleotide sequence homology between the high-molecular-weight (32S and 35S) RNA components of intracisternal A-particles from a neuroblastoma cell line and the 70S RNA fraction from M432, a type of retrovirus endogenous to the Asian mouse Mus cervicolor. M432 complementary DNA (cDNA) was hybridized to the extent of 30% by the A-particle RNAs. The hybrids showed a lower thermal stability (DeltaT(m), 7 degrees C) than those formed with homologous RNA. The reaction was commensurate with that found between M432 cDNA and divergent sequences in the M. musculus genome. The capacity to hybridize M432 cDNA was closely correlated with the concentration of A-particle sequences in the cytoplasmic RNA of several M. musculus cell types. The major RNA fraction of M432 virus showed a reciprocal partial reaction with the A-particle cDNA's; the virus, which was grown in NIH/3T3 (M. musculus) cells, also contained a small proportion of apparently authentic A-particle nucleotide sequences. A subset of A-particle sequences seemed to be almost totally lacking in the main M432 RNA. The A-particle cDNA's hybridized extensively with divergent sequences in M. cervicolor cellular DNA, indicating that this mouse species may contain not only the partially homologous M432 virogene, but also a more complete genetic equivalent of the intracisternal A-particle.

Animals↗
PubMed2025

Diversity and evolutionary history of endogenous retroviruses in the genome of Manis pentadactyla.

Endogenous retroviruses (ERVs), remnants of ancient viral infections integrated into host genomes, serve as invaluable molecular fossils for studying viral evolution. In this study, we performed a genomic analysis of the Chinese pangolin (Manis pentadactyla), identifying novel full-length endogenous retroviruses, designated as Manis pentadactyla ERVs (MPERVs). MPERVs span three retroviral genera: Alpha-, Beta-, and Gamma-retroviruses. Using genomic screening and phylogenetic analysis, we classified MPERVs and reconstructed their evolutionary history, uncovering evidence of complex recombination events and cross-species transmission. Estimated insertion times for MPERVs range from very recent to 18.38 million years ago. MPERVs exhibit diverse structural features, notably including conserved retroviral domains and functional motifs and highlighting their preservation across extensive evolutionary periods. These findings shed light on the evolutionary dynamics of ERVs in Chinese pangolin and suggest the potential for expanded host ranges among certain retrovirus genera.IMPORTANCEEndogenous retroviruses are unique viruses distinguished by the fact that they are retained as part of the host genome after an exogenous retrovirus infects the host. The Chinese pangolin, as a host with a long independent evolutionary history, likely holds valuable insights in its genome regarding retrovirus endogenization and transmission. In this study, we identified the footprints of exogenous retroviruses from three different genera in the pangolin genome: Alpharetrovirus, Betaretrovirus, and Gammaretrovirus. Additionally, by calculating the integration times of the pangolin's endogenous retroviruses and analyzing the domains of the three main functional proteins (GAG, POL, and ENV), we found that the insertions are relatively young. This suggests that these endogenous retroviruses infected the Chinese pangolin long before their endogenization. This study represents the exploration of endogenous retroviruses in the Chinese pangolin genome, expanding our understanding of endogenous retroviruses in mammals. Furthermore, our findings provide new evidence for the phenomenon of the cross-species transmission of retroviruses prior to endogenization.

Endogenous Retroviruses↗
PubMed2026

The role of transposable elements-endogenous retroviruses in embryonic development and regeneration.

Endogenous retroviruses (ERVs) are dynamically regulated across the lifespan and can function as context-dependent components of host gene-regulatory networks. During embryonic development, selected ERV-derived elements are co-opted to support zygotic genome activation, lineage specification, and placental development. In adult tissues, ERV-derived sequences can contribute to tissue and immune homeostasis, whereas potentially disruptive ERV activity is constrained by epigenetic mechanisms. During regeneration and somatic cell reprogramming, ERV and broader transposable-element programs undergo transient, locus-specific remodeling. In aging, the weakening of epigenetic and nuclear restraint can promote aberrant ERV derepression, inflammation, and functional decline. This review summarizes the diverse roles of ERVs across these contexts and discusses the challenges of defining locus-specific functions, resolving repetitive sequences, and developing safe ERV-targeted interventions.

Endogenous Retroviruses↗
PubMed2026

Human endogenous retroviruses leading to autoimmune diseases.

Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome and were long regarded as inert remnants of ancestral retroviral infections. Increasing evidence indicates that HERVs are active genomic elements capable of influencing transcriptional programs, modulating immune responses, and contributing to disease pathogenesis. Under physiological conditions, HERV expression is tightly controlled by epigenetic mechanisms; however, infections, chronic inflammation, aging, and diverse environmental stimuli can promote HERV reactivation. HERV-derived RNAs and proteins engage innate immune sensors and trigger antiviral-like responses through mechanisms of viral mimicry, leading to activation of type I interferon and other inflammatory pathways. HERV dysregulation has been associated with disease-relevant immune pathways. This review summarizes recent advances linking HERVs to autoimmune disease pathogenesis and discusses their potential translational relevance as biomarkers and therapeutic targets.

Humans↗
PubMed1979

In vivo induction of endogenous retroviruses in BALB/c mouse hepatocytes by successive treatments with carbon tetrachloride and bromodeoxyuridine.

The effects of bromodeoxyuridine (BrdUrd) incorporation into hepatocytes of carbon tetrachloride (CCl4)-induced regenerating liver of BALB/c mice on the induction of endogenous retroviruses was examined. From the nucliec acid hybridization studies, the maximum levels of hybridization were obtained for both N- and X-tropic BALB/c endogenous retrovirus specific [3H]-cDNAs with liver RNA from animals receiving BrdUrd at 40 and 44 h post-CCl4 treatment, and killed on the fourth day following BrdUrd injection. Media from NIH-3T3 (Swiss mouse) and mink cell cultures, infected with liver homogenates from animals treated as above, gave significant levels of reverse transcriptase activity. The observations made in the present study show that BrdUrd incorporation into cell DNA can cause induction of both N- and X-tropic endogenous retroviruses in BALB/c mouse hepatocytes in vivo, and such induction is probably a transient event.

Animals↗
PubMed2026

Discovery and evolution of endogenous retroviruses in the genome of crab-eating macaque (Macaca fascicularis).

Endogenous retroviruses (ERVs) are a dynamic and biologically significant component of vertebrate genomes, with integration events spanning deep evolutionary time. The crab-eating macaque (Macaca fascicularis) is an important non-human primate model for biomedical research because of its close phylogenetic relationship to humans and its conservation status as an endangered species. However, the ERV complement of its genome has not been systematically characterized. Using the current highest-quality chromosome-level genome assembly for this species, we performed a genome-wide, homology-based survey of relatively intact ERV proviruses in M. fascicularis. We identified 106 proviral loci distributed across all chromosomes. Phylogenetic reconstruction based on conserved reverse transcriptase domains classified these elements into β-, γ-, and unclassified lineages, with β- and γ-retroviral lineages predominating. LTR divergence-based dating indicated that these proviruses represent multiple waves of historical retroviral activity and span a broad range of integration ages. This curated dataset provides a high-confidence reference set for investigating the evolutionary history and genomic impact of preserved ERV proviruses in an endangered primate model; however, it does not include degraded ERV fragments or solo LTRs.

Animals↗
PubMed2025

Human endogenous retrovirus K (HERV-K) envelope structures in pre- and postfusion by cryo-EM.

Human endogenous retroviruses (HERVs) are remnants of ancient infections that comprise ~8% of the human genome. The HERV-K envelope glycoprotein (Env) is aberrantly expressed in cancers, autoimmune disorders, and neurodegenerative diseases, and is targeted by patients' own antibodies. However, a lack of structural information has limited molecular and immunological studies of the roles of HERVs in disease. Here, we present cryo-electron microscopy structures of stabilized HERV-K Env in the prefusion conformation, revealing a distinct fold and architecture compared to HIV and simian immunodeficiency virus. We also generated and characterized a panel of monoclonal antibodies with subunit and conformational specificity, serving as valuable research tools. These antibodies enabled structure determination of the postfusion conformation of HERV-K Env, including its unique "tether" helix, and antibody-bound prefusion Env. Together, these results provide a structural framework that opens the door to mechanistic studies of HERV-K Env and tools for its evaluation as a potential therapeutic target.

Cryoelectron Microscopy↗
PubMed2026

Distinct endogenous retroviruses are expressed in mutational subtypes of clear cell renal cell carcinoma and are linked to improved clinical outcomes.

Distinct mutations in chromatin regulators and aberrant expression of transposable elements (TEs), have been associated with clinical benefit to immunotherapy (IO) in specific clear cell renal cell carcinoma (ccRCC) clinical contexts. However, the relationship between mutations in chromatin regulators and TE expression, and their effect on clinical outcomes, are incompletely understood. Here, we identified TEs expressed in distinct mutational subtypes of ccRCC, with endogenous retroviruses (ERVs) comprising the majority of TEs observed. Of these, ERVs 544 and 2014 were upregulated in PBRM1 mutant samples. Patients with high expression of these ERVs and somatic PBRM1 mutations had improved progression-free survival with IO monotherapy, but not targeted therapy, and their upregulation associated with expression of innate immune pathways. Chromatin accessibility increased at ERV 544 and 2014 loci in PBRM1-deficient ccRCC cells, and ERV 544 and 2014 were upregulated upon in vitro PBRM1 knockout in ccRCC cell line clones. Broadly, our study supports a link between PBRM1 mutations, subsequent chromatin accessibility changes, and aberrant but immunoresponsive ERVs in ccRCC.

CP: cancer↗
PubMed1979

Evolutionary relatedness of viper and primate endogenous retroviruses.

A retrovirus previously isolated from a tumored Russell's viper is shown by molecular hybridization to be an endogenous virus of this reptilian species. Radio-immunologic techniques revealed that the viper retrovirus is immunologically and, hence, evolutionarily related to endogenous type D retorviruses of Old World primates. These findings extend the number of vertebrate classes possessing endogenous retroviruses and suggest that type D retroviruses may even be more widely distributed in nature than type C retroviruses.

Animals↗
PubMed2026

THE1 repeats: Ancient endogenous retroviruses rampaging behind sarcoid myopathy.

Transposon-like human element (THE1) repeats are classified as part of the ERVL (endogenous retrovirus-like) -MaLR family and were previously thought to be remnants derived from retroviral infections in the germ cells of ancient primates. At present, at least 60,561 THE1 repeats have been mapped in the human genome, and they are divided into four subfamilies: THE1A, THE1B, THE1C, and THE1D. Although these repeats are largely silenced in somatic cells through multiple mechanisms, some of them are known to influence gene functions and genomic structures, particularly under disease conditions. Recently, we happened to identify the CIR1 driven from THE1B in the individuals with sarcoid myopathy (SM), which is characterized by the non-caseating granulomatous inflammation recognized in skeletal muscles biopsy. Retrotrans-genomics based on the COFFEE method showed that various THE1B fusion transcripts (THE1B/FTs) and retrotransposon-associated genomic dynamics in muscle of SM, including (1) splicing of THE1B to neighborhood exons, (2) expression of THE1B associated long noncoding RNAs in the intergenic regions, (3) ectopic expression of tissue specific transcripts driven by THE1B in SM, and (4) identification of a read through transcript, SIRPB1-SIRPD. Seven of eight THE1B/FTs downregulated by tofacitinib in cutaneous sarcoidosis were confined to the granuloma associated macrophage in sarcoidosis. The remaining transcript, SMFT4 exhibited stronger expression in mesenchymal stem cells. In addition, ectopic co-expression of canonical and LINE1 and THE1A-exonizing IL23R transcripts were identified in SM. This directory of THE1B/FTs in SM may serve as a fundamental molecular basis for understanding the pathogenesis of sarcoidosis.

Journal Article↗
PubMed2026

Discovery and Engineering of a Rat Endogenous Retrovirus Reverse Transcriptase for Efficient Prime Editing.

CRISPR-based prime editors (PEs) install precise edits into genomic DNA without generating double-strand breaks. Their editing efficiency is highly dependent on reverse transcriptases (RTs), but efficient RT candidates remain limited. Here, we identified 19 novel active RTs by screening 558 candidates. Among them, RERV-RT, derived from Rattus norvegicus, exhibited the highest activity. Through structure-guided engineering and deep mutational scanning, we developed an optimized variant, enRERV-RT, which outperforms conventional M-MLV-RT-based PE systems by 1.20-fold in mammalian and plant cells, and by 1.88-fold at hard-to-edit loci, while enabling precise multiplex editing of functionally relevant genes. Additionally, we developed a high-throughput platform, TRAP-seq-PE, to systematically evaluate prime editor performance. Across diverse mutation types, we found that PE systems based on enRERV-RT exhibited higher editing efficiencies than those based on M-MLV-RT. Collectively, our work establishes a versatile, high-efficiency PE system, thereby facilitating advances in clinical gene therapy and precise crop breeding.

Animals↗
PubMed1979

Selective transcription of genomic sequences common to both N- and X-tropic endogenous retroviruses in BALB/c mouse tissues.

Total RNAs from four BALB/c mouse tissues, containing mostly non-dividing cells (liver and kidney) or variable proportions of dividing cells (uterus and embryo) were analysed for sequences complementary to 3H-DNA transcripts synthesized from BALB/c endogenous. N- and X-tropic retroviruses. Extensive transcription of virogene information was detected in the tissues examined, but such transcription was found to be mostly limited to the homologous regions of the two virus genomes. No additivity of hybridization values could be detected when RNAs from two different tissues were mixed, which suggests that BALB/c mouse liver, kidney, uterus and embryo transcribe a common set of nucleic acid sequences of the homologous regions of the N- and X-tropic viral genomes, in addition to other sequences of the same region that are specific for indiviual tissues.

Animals↗
PubMed1979

Identification of murine endogenous xenotropic retrovirus in cultured multicellular tumour spheroids from nude-mouse-passaged nasopharyngeal carcinoma.

After nude-mouse-passage, a carcinoma of the nasopharynx was found to contain a few scattered C-type retrovirus particles. Culture of this nude-mouse-grown material over solid agar allowed the human tumour cells to grow as multicellular spheroids which increased in number by budding and could be subcultured for up to 6 months. Within the spheroids the human tumour cells expressed increased retrovirus replication and large numbers of C-type particles were observed. Treatment with a halogenated pyrimidine further enhanced the virus production. This tissue culture system provided sufficient virus production for the identification of the retrovirus as an endogenous xenotropic murine leukaemia virus and not a human agent.

Animals↗
PubMed1979

The distribution of endogenous chicken retrovirus sequences in the DNA of galliform birds does not coincide with avian phylogenetic relationships.

The chicken is a domesticated form of Red Jungle-fowl (Gallus gallus), which belongs to the Pheasant family (Phasianidae) within the order Galliformes. Domestic chickens carry the genome of the endogenous retrovirus RAV-O as DNA sequences integrated into host chromosomes transmitted through the germ line. We have examined the presence and distribution of RAV-O-related sequences in the DNA of Red Junglefowl and other closely related species of Junglefowl, as well as more distantly related Pheasants and Quail. DNA sequences homologous to RAV-O were analyzed by molecular hybridization in liquid and after electrophoresis of restriction endonuclease fragments. The presence of RAV-O-related sequences in avian DNA does not correlate with phylogenetic relationships. Under stringent conditions of hybridization in liquid, DNA sequences homologous to RAV-O cDNA were detected at high levels (greater than 80% homology( only in the genomes of the domestic chicken and its phylogenetic ancestor, the Red Junglefowl (Gallus gallus). The DNA of two other species of Gallus (G. sonnerati, Sonnerat's Junglefowl and G. varius, Green Junglefowl), of Ring-necked Pheasant and of Japanese Quail contained sequences with less than 10% homology to RAV-O cDNA. Under conditions permitting mismatching, however, Ring-necked Pheasant DNA hybridized up to 50% of the RAV-O cDNA, and Quail DNA 24%, whereas the extent of hybridization to Sonnerat's and Green Junglefowl DNA was not markedly increased. Analysis of restriction enzyme digests revealed several distinct fragments of DNA hybridizing to chick retrovirus cDNA in both Red Junglefowl and domestic chicken, and multiple fragments in DNA from two species of Phasianus. No fragments with sequences related to chicken retroviruses were found, however, in digests of DNA prepared from Sonnerat's, Ceylonese and Green Junglefowl, from two other Pheasant genera (Chrysolophus and Lophura), or from one Quail genus (Coturnix). Thus the DNA of three Junglefowl species closely related to Gallus gallus lacked RAV-O sequences while the DNA of more distantly related Phasianus species showed significant homology. These results show that RAV-O-related sequences have not diverged together with the normal host genes during the evolution of the Phasianidae. Although RAV-O sequences are endogenous in all domestic chickens and Red Junglefowl studied thus far, it appears that the RAV-O genome has been introduced relatively recently into the germ line of Gallus gallus, following speciation but before domestication, and independently of the related sequences found in members of the genus Phasianus.

Alpharetrovirus↗