• BMB Reports
• /
• v.54 no.7
• /
• pp.368-373
• /
• 2021

The vertebrate genome contains an endogenous retrovirus that has been inherited from the past millions of years. Although approximately 8% of human chromosomal DNA consists of sequences derived from human endogenous retrovirus (HERV) fragments, most of the HERVs are currently inactive and noninfectious due to recombination, deletions, and mutations after insertion into the host genome. Several studies suggested that Human endogenous retroviruses (HERVs) factors are significantly related to certain cancers. However, only limited studies have been conducted to analyze the expression of HERV derived elements at protein levels in certain cancers. Herein, we analyzed the expression profiles of HERV-K envelope (Env) and HERV-R Env proteins in eleven different kinds of cancer tissues. Furthermore, the expression patterns of both protein and correlation with various clinical data in each tissue were analyzed. The expressions of both HERV-K Env and HERV-R Env protein were identified to be significantly high in most of the tumors compared with normal surrounding tissues. Correlations between HERV Env expressions and clinical investigations varied depending on the HERV types and cancers. Overall expression patterns of HERV-K Env and HERV-R Env proteins were different in every individual but a similar pattern of expressions was observed in the same individual. These results demonstrate the expression profiles of HERV-K and HERV-R Env proteins in various cancer tissues and provide a good reference for the association of endogenous retroviral Env proteins in the progression of various cancers. Furthermore, the results elucidate the relationship between HERV-Env expression and the clinical significance of certain cancers.

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

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

• Reproductive and Developmental Biology
• /
• v.32 no.2
• /
• pp.105-110
• /
• 2008

The endogenous retrovirus-like elements (HERVs) found on several human chromosomes are somehow involved in gene regulation, especially during the transcription level. HERV-H, located on chromosome Xp22, may regulate gastrin-releasing peptide receptor (GRPR) in connection with diverse diseases. By suppression subtractive hybridization screen on SV40-immortalized lung fibroblast (WI-38 VA-13), we discovered that expression of HERV-HX2, a clustered HERV-H sequence on chromosome X, was upregulated in immortalized lung cells, compared to that of normal cells. Expression of HERV-HX2 was then analyzed in various cell lines, including normal somatic cells, cancer cells, SV40-immortalized cells, and undifferentiated and differentiated human embryonic stem cells. Expression of HERV-HX2 was specifically upregulated in continuously-dividing cells, such as cancer cells and SV40-immortalized cells. Especially, HERV-HX2 in HeLa cells was highly upregulated during the S phase of the cell cycle. Similar results were obtained in hES cells, in which undifferentiated cells expressed more HERV-HX2 mRNA than differentiated hES cells, including neural precursor and endothelial progenitor cells. Taken together, our results suggest that HERV-HX2 is upregulated in cancer cells and undifferentiated hES cells, whereas downregulated as differentiation progress. Therefore, we assume that HERV-HX2 may playa role on proliferation of cancer cells as well as differentiation of hES cells in the transcriptional level.

• Animal cells and systems
• /
• v.6 no.2
• /
• pp.167-170
• /
• 2002

The long terminal repeats (LTRs) of human endogenous retrovirus (HERV) have been found to be coexpressed with sequences of closely located genes. It has been suggested that the LTR elements have contributed to the structural change or genetic variation of human genome connected to various diseases and evolution. We examined the HERV-W LTR elements in various cancer cells (2F7, A43l , A549, HepG2, MIA-PaCa-2, PC-3, RT4, SiHa, U-937, and UO-31). Using genomic DNA from the cancer cells, we performed PCR amplification and identified twelve new HERV-W LTR elements. Those LTR elements showed a high degree of sequence similarity (88-99％) 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. Three HERV-W LTR elements (RT4-2, A43l-1, and UO3l-2) belonged to Group 1, whereas nine LTR elements (2F7-2, A549-1, A549-3, HepG2-3, MP2-2, PC3-1, SiHa-8, SiHa-10, and U937-1) belonged to Group 11. Taken together, our new sequence data of the HERV-W LTR elements may contribute to an understanding of tissue-specific cancer by genomic instability of LTR integration.

• Journal of Life Science
• /
• v.10 no.2
• /
• pp.45-49
• /
• 2000

Long terminal repeat (LTR) of human endogenous retrovirus K family (HERV-K) has been found to be coexpressed with sequences of closely located genes. We examined the transcribed HERV-K LTR elements in human liver and kidney tissues. Using the cDNA synthesized from mRNA of human liver and kidney, we performed PCR amplification and identified six HERV-K LTR elements. Those LTR elements showed a high degree of sequence similarity (93.3∼96.6%) with human-specific LTR. A phylogenetic tree obtained by the neighbor-joining method revealed that HERV-K LTR elements (Liv-1, 2, 3 and Kid-1, 2, 3) were belonged to group I. Our data suggests that HERV-K LTR elements are active on human liver and kidney tissues and may represent a source of genetic variation connected to human disease.

• Journal of Life Science
• /
• v.11 no.2
• /
• pp.83-86
• /
• 2001

The long terminal repeat (LTR) elements of human endogenous retrovirus (HERV) have been found to be coexpressed 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 genomic DNAs derived from schizophrenia, we performed PCR amplification and identified six HERV-W LTR elements. Those LTR elements showed a high degree of sequence similarity (87.7-99.5%) with HERV-W LTR (AF072500). Sequence analysis of the HERV-W LTR elements revealed that clone W-sch1 showed identical sequence with the AC003014 (PAC clone RP1-290B4) derived from human Xq23. Clone W-sch2 was closely related to the AC0072442 derived from human Y chromosome by phylogenetic analysis. Our data suggest that new HERV-W LTR elements in schizophrenia may be very useful for further studies to understand neuropsychiatric diseases.

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

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

• Journal of Life Science
• /
• v.13 no.3
• /
• pp.291-297
• /
• 2003

A human endogenous retroviral family (HERV-W) has recently been described that is related to multiple sclerosis-associated retrovirus (MSRV) sequences that have been identified in particles recovered from monocyte cultures from patients with multiple sclerosis. Two pol fragments (HWP-FB10 and HWP-FBl2) of HERV-W family were identified and analysed by the PCR approach with cDNA library of human fetal brain. They showed 89 percent nucleotide sequence similarity with that of the HERV-W (accession no. AF009668). Deletion/insertion or point mutation in the coding region of the pol fragments from human fetal brain resulted in amino acid frameshift that induced a mutated protein. Phylogenetic analysis of the HERV-W family from GenBank database indicates that the HWP-FB10 is very closely related to the AC000064 derived from human chromosome 7q21-q22. Further studies on the genetic relationship with neighbouring genes and functional role of these new HERV-W pol sequences are indicated.