• Animal cells and systems
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• v.5 no.2
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• pp.133-137
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• 2001

Long terminal repeats (LTRs) of the human endogenous retrovirus K family (HERV-K) have been found to be coexpressed with sequences of genes closely located nearby. We examined transcribed HERV-K LTR elements in human brain tissue. Using cDNA synthesized from mRNA of the human brain, we performed PCR amplification and identified ten HERV-K LTR elements. These LTR elements showed a high degree of sequence similarity (92.4-99.7%) with the human-specific LTR elements. A phylogenetic tree obtained by the neighbor-joining method revealed that HERV-K LTR elements could be divided into two groups through evolutionary divergence. Some HERV-K LTR elements (HKL-B7, HKL-B8, HKL-B10) belonging to the group II from human brain cDNA were closely related to the human-specific HERV-K LTR elements. Our data suggest that HERV-K LTR element are active in the human brain; they could conceivably play a pathogenic role in human diseases such as psychosis.

• Molecules and Cells
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• v.44 no.12
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• pp.861-878
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• 2021

The human genome contains many retroviral elements called human endogenous retroviruses (HERVs), resulting from the integration of retroviruses throughout evolution. HERVs once were considered inactive junk because they are not replication-competent, primarily localized in the heterochromatin, and silenced by methylation. But HERVs are now clearly shown to actively regulate gene expression in various physiological and pathological conditions such as developmental processes, immune regulation, cancers, autoimmune diseases, and neurological disorders. Recent studies report that HERVs are activated in patients suffering from coronavirus disease 2019 (COVID-19), the current pandemic caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. In this review, we describe internal and external factors that influence HERV activities. We also present evidence showing the gene regulatory activity of HERV LTRs (long terminal repeats) in model organisms such as mice, rats, zebrafish, and invertebrate models of worms and flies. Finally, we discuss several molecular and cellular pathways involving various transcription factors and receptors, through which HERVs affect downstream cellular and physiological events such as epigenetic modifications, calcium influx, protein phosphorylation, and cytokine release. Understanding how HERVs participate in various physiological and pathological processes will help develop a strategy to generate effective therapeutic approaches targeting HERVs.

• Journal of Life Science
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• v.10 no.1
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• pp.32-36
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• 2000

Solitary long terminal repeats(LTRs) of human endogenous retrovirus K family(HERV-K) have been found to be coexpressed with sequences of closely located genes. It has been suggested that HERV-K LTR-like elements entered the primate genome approximately 33-40 million years ago. WE investigated the presence of HERV-K LTR elements in New World monkeys using PCR amplification. Six LTR elements of HERV-K family were identified from New World monkeys, represented by the squirrel and night monkeys. They showed a high degree of sequence homology(96-99%) with the human-specific HERV-K LTR elements. Phylogenetic analysis reveals that an LTR element (SM-1) from the squirrel monkey and another LTR element (NM-1) from the night monkey are very closely related to the human-specific HERV-K LTR elements with low degree of divergence. This finding suggests that some of LTR elements of HERV-K family have recently been proliferated in New World monkeys. A sequence in chromosome Xq26(AL034407) \ulcorner contains an HERV-K LTR element was shown to be present in the human genome, but is absent in the bonobo, chimpanzee, gorilla, orangutan, and gibbon. It has more than 99% homology to other human-specific HERV-K LTR elements. This sequence thus represents and isolated insertion of an evolving class of elements that may have made a particular contribution to human genomic plasticity.

• Journal of Life Science
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• v.11 no.4
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• pp.379-384
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• 2001

Long terminal repeats(LTRs) of the human endogenous retrovirus(HERV) heve been found to be coexpresed with genes located nearby. It has been suggested that the LTR elements have contributed to the genetic variation of human genome connected to various diseases. Recently, HERV-W family was identified in the cerebrospinal fluids and brains of individuals with schizophrenia. Using cHNA library derived from human fetal brain, we performed PCR amplification and identified seven new HERV-W LTR elements. Those LTR elements showed a high degree of sequence similarity(98∼99%) with HERV-W (AF072500). A phylogentic tree obtained by the neighbor-joining method revealed that seven new HERV-W LTR elements(FB-1, 2, 4, 8, 9, 10, 12) were closely related to the AX000960, AF072504, and AF072506 from Gen Bank database. Our data suggest that several copy numbers of the HERV-W LTR elements are expressed in human feta brain and may contribute to an understanding of biological function connected to neuropsychiatric diseases.

• The Journal of Korean Society of Virology
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• v.29 no.2
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• pp.107-118
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• 1999

To characterize the molecular nature of human immunodeficiency virus (HIV)-1, we determined the full-length HIV-1 sequences from cultured peripheral blood mononuclear cells (PBMC) of a Korean long-term nonprogressor (LTNP). Without antiretroviral therapy, the individual has maintained CD4+ T counts over $500/{\mu}l$ from 1989 to 1999. Plasma viral RNA copy was 992 U/ml in 1998. Culture supernatant showed positive from culture days 9. A series of 9 overlapping PCR products were amplified from cultured PBMC and cloned About 9.2 kb from R of 5' LTR to R of 3' LTR was determined by automated sequencing. The G-to-A hypermutations were shown throughout the entire region. As a result of G to A hypermutations, premature stop codon was found in integrase coding region. Though there was no recombination between subtypes over all genomes, TATA box in both LTRs was TAAAA which is detected in subtype E instead of TATAA in subtype B. And, there were nucleotide GC insertion between $NF-{\kappa}B$ I and Sp1 III, and duplication of $TCF-1{\alpha}$ in LTR. We could not find any deletion of amino acid in Nef, Gag, Pol and Env gene. This study is the first report on molecular nature of full genomes of HIV-1 isolated in Korea.

• Animal cells and systems
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• v.5 no.3
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• pp.243-246
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• 2001

Human endoqenous retroviral long terminal repeats (LTRs) have been found to be coexpressed with sequences of genes closely located nearby. It has been suggested that the LTR elements have contributed to structural changes or genetic variations of human genome connected to various diseases and evolution. Using cDNA library derived from placenta tissue, we performed PCR amplification and identified five new HERV-W LTR elements. Those LTR elements showed a high degree of sequence similarity (98-99%) with HERV-W LTR (AF072500). A phylogenetic tree obtained by the neighbor-joining method revealed that HERV-W LTR elements could be mainly divided into two groups through evolutionary divergence. Five new HERV-W LTR elements (pla-1, 4, 5, 6, 7) belonged to the group I with AX000960, AF072504, and AF072506 from GenBank database. The data suggest that several copy numbers of the HERV-W LTR elements are transcribed in placenta and may contribute to the understanding of biological function such as human placental morphogenesis.

• Molecules and Cells
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• v.26 no.1
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• pp.53-60
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• 2008

We characterized the human endogenous retrovirus (HERV-W) family in humans and primates. In silico expression data indicated that 22 complete HERV-W families from human chromosomes 1-3, 5-8, 10-12, 15, 19, and X are randomly expressed in various tissues. Quantitative real-time RT-PCR analysis of the HERV-W env gene derived from human chromosome 7q21.2 indicated predominant expression in the human placenta. Several copies of repeat sequences (SINE, LINE, LTR, simple repeat) were detected within the complete or processed pseudo HERV-W of the human, chimpanzee, and rhesus monkey. Compared to other regions (5'LTR, Gag, Gag-Pol, Env, 3'LTR), the repeat family has been mainly integrated into the region spanning the 5'LTRs of Gag (1398 bp) and Pol (3242 bp). FISH detected the HERV-W probe (fosWE1) derived from a gorilla fosmid library in the metaphase chromosomes of all primates (five hominoids, three Old World monkeys, two New World monkeys, and one prosimian), but not in Tupaia. This finding was supported by molecular clock and phylogeny data using the divergence values of the complete HERV-W LTR elements. The data suggested that the HERV-W family was integrated into the primate genome approximately 63 million years (Myr) ago, and evolved independently during the course of primate radiation.

• Molecules and Cells
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• v.26 no.4
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• pp.404-408
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• 2008

The genome of replication-competent BERV ${\gamma}4$ provirus, which is the most abundant ERV family in the bovine genome, was characterized in detail. The BERV ${\gamma}4$ genome showed that BERV ${\gamma}4$ harbors 8576 nucleotides and has the typical 5'-long terminal repeat (LTR)-gag-pro-pol-env-LTR-3' retroviral organization with a long leader region positioned before the gag open reading frame. Multiple sequences analysis showed that the nucleotide difference between 5' and 3' LTRs was 4.2% (mean value 0.042) in average, suggesting that the provirus formed at most 13.3 million years ago. Gag separated by a stop codon from pro-pol in the same reading frame, while env resides in another reading frame lacking of a functional surface domain. According to the current bovine genome sequence assembly, the full-length BERV ${\gamma}4$ provirus sequences were only found in the chromosomes 1, 2, 6, 10, 15, 23, 26, 28, X, and unassigned, although the partial sequences almost evenly distributed in the entire bovine genome. This is the first detailed study describing the genome structure of BERV ${\gamma}4$, the most abundant ERV family present in bovine genome. Combined with our recent reports on characterization of ERVs in bovine, this study will contribute to illuminate ERVs in the cattle of which no information was previously available.

• Journal of Life Science
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• v.27 no.10
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• pp.1215-1224
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• 2017

Until now, various oncogenic pathways were idenfied. The accumulation of DNA mutation induces genomic instability in the cell, and it makes cancer. The development of bioinformatics and genomics, to find the precise and reliable biomarker is available. This biomarker could be applied the early-dignosis, prediction and convalescence of cancer. Recently, Transposable elements (TEs) have been attracted as the regulator of genes, because they occupy a half of human genome, and the cause of various diseases. TEs induce DNA mutation, as well as the regulation of gene expression, that makes to cancer development. So, we confirmed the relationship between TEs and colon cancer, and provided the clue for colon cancer biomarker. First, we confirmed long interspersed nuclear element-1 (LINE-1), Alu, and long terminal repeats (LTRs) and their relationship to colon cancer. Because these elements have large composition and enormous effect to the human genome. Interestingly, colon cancer specific patterns were detected, such as the hypomethylation of LINE-1, LINE-1 insertion in the APC gene, hypo- or hypermethylation of Alu, and isoform derived from LTR insertion. Moreover, hypomethylation of LINE-1 in proto-oncogene is used as the biomarker of colon cancer metastasis, and MLH1 mutation induced by Alu is detected in familial or hereditary colon cancer. The genes, effected by TEs, were analyzed their expression patterns by in silico analysis. Then, we provided tissue- and gender-specific expression patterns. This information can provide reliable cancer biomarker, and apply to prediction and diagnosis of colon cancer.