• 생명과학회지
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• 제31권8호
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• pp.771-777
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• 2021

인간 내생 레트로바이러스(Human Endogenous Restrovirus, HERV)는 수백만년전 인간의 유전체에 삽입되었으며 이후 오랜 세월을 거치며 재조합, 결실 및 돌연변이 등 여러 원인에 의해 더 이상 활성화된 바이러스로 역할을 하지 못하고 감염되지 않는다. 하지만 HERV는 최근 연구들은 HERV 유래 인자들이 실제 생리현상 및 암을 비롯한 특정 질환에 관여 하고 있다는 것을 보여 주었다. HERV와 관련된 여러가지 생리 현상 중 염증반응에 초점을 맞추어 고찰해 볼 필요가 있다. HERV는 류마티스, 다발성 경화증, 근위축성 측삭경화증, 쇼그렌 증후군 같은 자가면역질환을 비롯한 여러 염증질환에 직접적으로 관여하는 것으로 보고 되고 있다. HERV의 염증 조절 기작으로는 HERV 유래 인자들이 비특이적 선천성 면역과정을 유발할 가능성과 HERV 유래의 RNA와 단백질이 특정 수용체를 통해 선택적 신호전달기작을 유발할 가능성을 고려 할 수 있다. 하지만 어떠한 방식으로 잠재되어 있던 HERV가 염증반응에서 활성화 되는지 또한 HERV와 관여된 인자들과 신호기작들이 어떠한 것들이 있는지 등 HERV의 인자들이 염증반응을 조절하는 기작에는 아직 많은 것들이 밝혀지지 않아 질병 발병에 대한 연구에 어려움이 있는 실정이다. 본 리뷰에서는 HERV 관련 자가 면역질환을 소개하고 염증반응 조절 기작에 관한 HERV의 분자수준에서의 작용 메커니즘을 제안 하고자 한다.

• BMB Reports
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• 제54권7호
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• pp.368-373
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• 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.

• 생명과학회지
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• 제11권5호
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• pp.400-404
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• 2001

최근 새로운 인간 내생 레트로바이러스 패밀리(HERAV-S)가 인간의 X 염색체상에서 동정 되었다. 그 길이는 6.7kb 이며 LTR-gag-pol-env-LTR의 일반적인 레트로바이러스의 구조를 가졌다. PCR 방법과 염기서열분석을 통하여 인간 게놈 DNA에서 HERV-S LTR 패밀리를 동정하였다. 네 개의 LTR엘리먼트(HSL-1, HSL-5, HSL-10, HSL-11)가 동정 되었으며, 이들은 HERV-S LLR 패밀리는 영장류의 진화과정에서 진화적인 분기를 통해 주된 2개의 그룹으로 나뉘어졌다. 영장류에서 이러한 HERV-S LTR들의 연구가 이루어진다면 이들의 영장류 게놈 내의 삽입시기를 알 수 있고 또한 인류의 진화를 이해하는데 크게 이바지 할 것이다.

• Animal cells and systems
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• 제6권2호
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• pp.167-170
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• 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.

• Animal cells and systems
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• 제5권2호
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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.

• Journal of Life Science
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• 제10권1호
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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.

• Reproductive and Developmental Biology
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• 제32권2호
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• pp.105-110
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• 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.

• 생명과학회지
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• 제25권4호
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• pp.481-485
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• 2015

수백만 년 전부터 인간의 유전체에는 retrovirus의 유전자들이 삽입되기 시작하였다. 이러한 retrovirus의 유전자들은 결실 혹은 nonsense mutation등 여러 영향으로 지금은 더 이상 활동성 있는 바이러스로서의 역할을 못하는 흔적으로만 남아 있는 형태로 존재하며 이러한 내생(endogenous) retrovirus를 human endogenous retrovirus (HERV)라 부른다. HERV의 각 유전자들은 완성된 활동성을 지닌 바이러스를 만들어 내지는 못하지만 여전히 부분적으로 발현이 가능하고 심지어는 바이러스 particle 까지 만들어지는 것이 관찰되었다. 이러한 내성 retrovirus 에 반해 실질적으로 감염되고 활동하여 질병을 야기하는 외인성(exogenous) retrovirus들이 있는데 이 중 human immunodeficiency virus (HIV)는 인간의 생명을 위협하는 대표적 바이러스로 가장 많이 연구되고 있는 바이러스중의 하나이다. 최근 흔적으로만 존재하는 것으로 보고된 HERV가 실질적으로 활성화된 바이러스인 HIV의 감염에 의해 활성화되고 발현이 증가할 뿐 아니라 HIV 감염의 여러 과정에 관여하고 있다는 연구 결과가 보고되고 있다. 또한 이러한 현상을 이용하여 HIV의 백신 및 치료 방법으로 HERV를 이용하고자 하는 시도가 활발히 이루어지고 있다. 이 리뷰에서는 HIV 감염에 의한 HERV의 활성화 및 관련 상호 기작에 관한 연구를 소개하고 HERV를 이용한 HIV의 백신 및 치료제 개발을 위한 시도들을 함께 소개하고자 한다.

• Journal of Microbiology and Biotechnology
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• 제12권3호
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• pp.508-513
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• 2002

Human endogenous retroviral long terminal repeats (LTRs) have been found to be coexpressed with sequences of genes located nearby. It has been suggested that the LTR elements have contributed to the structural change or genetic variation of human genome connected to various diseases. The HERV-W family has been identified in the cerebrospinal fluids and brains of individuals with schizophrenia. Using a cDNA library derived from a human brain, the HERV-W LTR elements were examined and five new LTR elements were identified. These elements were examined using a YAC clone panel from the Xq21.3 region linked to psychosis that was replicated on the Y chromosome after the separation of the chimpanzee and human lineages. Fourteen elements of the HERV-W LTR were identified in that region. Those LTR elements showed a high degree of sequence similarity ($91.8-99.5\%$) with previously reported HERV-W LTR. A phylogenetic tree obtained from the neighbor-joining method revealed that new HERV-W LTR elements were closely related to the AXt000960, AF072504, and AF072506 from the GenBank database. The data indicates that several copy numbers of the HERV-W LTR elements exist on the Xq21.3 region and are also expressed in the human brain. These LTR elements need to be further investigated as potential leads to neuropsychiatric diseases.

• Journal of Life Science
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• 제11권2호
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• pp.83-86
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• 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.