Quantitative analysis of the HERV pol gene in human tissues

안궁,한규동,김희수 한국유전학회 2011 Genes & Genomics Vol.33 No.4

Human endogenous retroviruses (HERVs) have been associated with cancer pathogenesis due to their close homology to exogenous tumorigenic retroviruses. The expression pattern of HERVs could provide important insights into the pathogenic state between HERVs and various cancers. Using the RetroTector10 program, we identified four full-length HERV elements (HML4, HERV-T, HERV-F, and HERV-R) that contain pol genes with reverse transcriptase sub domains. Through a quantitative real-time RT-PCR approach, we investigated expression levels of their pol genes in various human tissues including tumor and adjacent normal tissue samples. The HML4 and HERV-T pol genes were ubiquitously expressed in all human tissues, whereas the HERV-F pol gene was only expressed in the human placenta. In further analysis, we compared expression levels of the HERV pol genes in normal tissues and their corresponding tumor tissues. Interestingly, the HERV-F pol gene showed high expression in lung tumors while its expression level was very low in normal lung tissues (p-value = 0.007). In addition, the HERV-R pol gene showed a higher expression in stomach tumors than in normal tissues (p-value = 0.044). Thus, we suggest that the expression profiling of HERV-F and HERV-R pol genes could be used as a molecular marker system to detect human stomach and lung cancers, respectively.

Identification of pol Gene Mutation among BLV Proviruses Found in the Southern Province of Korea

Kwon, Oh-Sik The Korean Society of Virology 2000 Journal of Bacteriology and Virology Vol.29 No.1

Bovine leukemia virus (BLV) is an etiological agent of chronic diseases in cows worldwide. The BLV is one of retroviruses that contain a multi-functional enzyme, reverse transcriptase produced from the pol gene in its genome. We have sequenced some regions in the pol gene of BLV proviruses found in the Southern province of Korea from samples that turned out to be BL V positives by a PCR analysis. On the 5' side of the BLV pol gene (polymerase region), it was found that there were four leucines located at every 7 amino acids. They can form a leucine zipper motif that was not same as the pol gene of Japanese BLV isolate. The sequencing result of the proviral pol gene in Korean-type BLV also revealed some mutations leading to amino acid changes such as $CCT(Pro){\to}CTC(Leu)$, $AAT(Asn){\to}AAA(Lys)$, and non-sensible variations i.e., $TCT(Ser){\to}TCC(Ser)$, $ATT(Ile){\to}ATC(I1e)$ and $ACG(Thr){\to}ACA(Thr)$. On the 3' side of the pol gene (integrase region), some nucleotide sequences were mutated and led to amino acid changes. Among them, a mutation, $GAA(Glu){\to}GAC(Asp)$ occurred in many Korean-type BLV proviruses was very interesting because the amino acid was regarded as one of the most conserved amino acids in the retroviral integrase. It was also notable that the mutation on any leucine residue did not occur, in spite of its frequent appearance.

A Study on DNA Sequences and Mutation of Integrase Region of Korean-type Bovine Leukemia Virus (BLV) pol Gene

Kwon, Oh-Sik,Kang, Jung-Soon,Park, Hyun-Jin,Yoo, Min The Korean Society for Biomedical Laboratory Scien 2004 Journal of biomedical laboratory sciences Vol.10 No.1

Bovine leukemia virus (BLV) is a causative agent for lymphoma disease in cattle including cows worldwide. BLV shares similar virion structure and characteristics with other retroviruses. The pol gene of the BLV genome produced reverse transcriptase (RT) and integrase (IN) for important roles for BLV genome integration into host cell chromosomes that is known to be coded in the 3' side of the BLV pol gene (one third portion). In this study, we have sequenced 978 bp in the 3' side of the BLV pol gene from BLV 10C3 in order to determine the BLV IN region of it. And we compared it to the nucleotide sequences of an Australian BLV isolate. As a result, nucleotide sequences of the IN region of the Korean-type BLV pol gene were mutated at a rate of 3.7%. We can confirm that the typical mutations are such as Arg (AGG) $\rightarrow$ Lys (AAG), Thr (ACG) $\rightarrow$ Met (ATG), Ile (ATT) $\rightarrow$ Val (GTT), Asn (ACC) $\rightarrow$ His (CAC), Phe (TTT) $\rightarrow$ Leu (TTG) and Asn (ACC) $\rightarrow$ Asp (GAC). From the analysis of the sequencing data, we were able to determine the zinc-finger-like "HHCC" motif in the amino terminus of BLV IN, that was H-$X_3$-H-$X_{25}-C-X_2$-C. It was also found the DD35E motif in the IN catalytic domain as D-$X_{56}$-D-$X_{35}$-E. It fits very well to the consensus sequences of retroviral IN as well as HHCC motif.

A Study on DNA Sequences and Mutation of Integrase Region of Korean-type Bovine Leukemia Virus (BLV) pol Gene

Oh-Sik Kwon,Jung-Soon Kang,Hyun-Jin Park,Min Yoo 대한의생명과학회 2004 Biomedical Science Letters Vol.10 No.1

Bovine leukemia virus (BLV) is a causative agent for lymphoma disease in cattle including cows worldwide. BLV shares similar virion structure and characteristics with other retroviruses. The pol gene of the BLV genome produced reverse transcriptase (RT) and integrase (IN) for important roles for BLV genome integration into host cell chromosomes that is known to be coded in the 3' side of the BLV pol gene (one third portion). In this study, we have sequenced 978 bp in the 3' side of the BLV pol gene from BLV 10C3 in order to determine the BLV IN region of it. And we compared it to the nucleotide sequences of an Australian BLV isolate. As a result, nucleotide sequences of the IN region of the Korean-type BLV pol gene were mutated at a rate of 3.7%. We can confirm that the typical mutations are such as Arg (AGG) → Lys (AAG), Thr (ACG) → Met (ATG), Ile (ATT) → Val (GTT), Asn (ACC) → His (CAC), Phe (TTT) → Leu (TTG) and Asn (ACC) → Asp (GAC). From the analysis of the sequencing data, we were able to determine the zinc-finger-like "HHCC" motif in the amino terminus of BLV IN, that was H-X₃-H-X₂?-C-X₂-C. It was also found the DD35E motif in the IN catalytic domain as D-X??-D-X₃?-E. It fits very well to the consensus sequences of retroviral IN as well as HHCC motif.

A Study on DNA Sequences and Mutation of Integrase Region of Korean-type Bovine Leukemia Virus (BLV) pol Gene

권오식,--,--,-- THE KOREAN SOCIETY FOR BIOMEDICAL LABORATORY SCIEN 2004 Journal of biomedical laboratory sciences Vol.10 No.1

Bovine leukemia virus (BLV) is a causative agent for lymphoma disease in cattle including cows worldwide. BLV shares similar virion structure and characteristics with other retroviruses. The pol gene of the BLV genome produced reverse transcriptase (RT) and integrase (IN) for important roles for BLV genome integration into host cell chromosomes that is known to be coded in the 3' side of the BLV pol gene (one third portion). In this study, we have sequenced 978 bp in the 3'side of the BLV pol gene from BLV 10C3 in order to determine the BLV IN region of it. And we compared it to the nucleotide sequences of an Australian BLV isolate. As a result, nucleotide sequences of the IN region of the Korean-type BLV pol gene were mutated at a rate of 3.7%. We can confirm that the typical mutations are such as Arg (AGG) → Lys(AAG), Thr (ACG) → Met (ATG), Ile (ATT) → Val (GTT), Asn (ACC) → His (CAC), Phe (TTT) → Leu (TTG) and Asn (ACC) → Asp (GAC). From the analysis of the sequencing data, we were able to determine the zinc-finger-like "HHCC" motif in the amino terminus of BLV IN, that was H-X_(3)-H-X_(25)-C-X_(2)-C. It was also found the DD35E motif in the IN catalytic domain as D-X_(56)-D-X_(35)-E. It fits very well to the consensus sequences of retroviral IN as well as HHCC motif.

Expression and promoter activity of endogenous retroviruses in the Olive flounder (Paralichthys olivaceus)

김희수,김원,남규휘,김정안,이희은,김우진,정형택 한국유전학회 2016 Genes & Genomics Vol.38 No.6

Olive flounder (Paralichthys olivaceus) is regarded as one of economical fish species in the world. Genome information of Olive flounder has been revealed by next generation sequencing. Endogenous retroviruses (ERVs) as a member of transposable elements have been involved in functional roles of various genes in variety organisms. In this study, we identified an Olive flounder ERV (OF-ERV5) using RepeatMasker program, and examined expression pattern of pol gene of OF-ERV5, which indicated the high expression in two kidney samples (head kidney and body kidney). In addition, the 50LTR sequences of OF-ERV5 are cloned into pGL4.11 vectors to confirm promoter activity. Luciferase assay indicated that the OF-ERV5_LTR showed promoter activity in both HepG2 and HINAE cell lines. These data could be of great use for further study to understand biological function of transposable elements in Oliver flounder.

Identification of pol Gene Mutation among BLV Proviruses Found in the Southern Province of Korea

Oh Sik Kwon 대한바이러스학회 2000 Journal of Bacteriology and Virology Vol.30 No.2

Identification and Expression Analyses of Equine Endogenous Retroviruses in Horses

김정안,김희수 한국분자세포생물학회 2017 Molecules and cells Vol.40 No.10

Endogenous retroviruses (ERVs) have been inte-grated into vertebrate genomes and have momentously affected host organisms. Horses (Equus caballus) have been domesticated and selected for elite racing ability over centuries. ERVs played an important role in the evolutionary diversification of the horse genome. In the present study, we identified six equine ERV families (EqERVs-E1, I1, M2, P1, S1, and Y4), their full-length viral open reading frames (ORFs), and elucidated their phylogenetic relationships. The divergence time of EqERV families assuming an evolutionary rate of 0.2%/Myr indicated that EqERV-S3 (75.4 million years ago; mya) on chromosome 10 is an old EqERV family and EqERV-P5 (1.2 Mya) on chro-mosome 12 is a young member. During the evolutionary diversification of horses, the EqERV-I family diverged 1.7 Mya to 38.7 Mya. Reverse transcription quantitative real-time PCR (RT-qPCR) amplification of EqERV pol genes showed greater expression in the cerebellum of the Jeju horse than the Thoroughbred horse. These results could contribute further dynamic studies for horse genome in relation to EqERV gene function.

Identification and Expression Analyses of Equine Endogenous Retroviruses in Horses

Gim, Jeong-An,Kim, Heui-Soo Korean Society for Molecular and Cellular Biology 2017 Molecules and cells Vol.40 No.10

Endogenous retroviruses (ERVs) have been integrated into vertebrate genomes and have momentously affected host organisms. Horses (Equus caballus) have been domesticated and selected for elite racing ability over centuries. ERVs played an important role in the evolutionary diversification of the horse genome. In the present study, we identified six equine ERV families (EqERVs-E1, I1, M2, P1, S1, and Y4), their full-length viral open reading frames (ORFs), and elucidated their phylogenetic relationships. The divergence time of EqERV families assuming an evolutionary rate of 0.2%/Myr indicated that EqERV-S3 (75.4 million years ago; mya) on chromosome 10 is an old EqERV family and EqERV-P5 (1.2 Mya) on chromosome 12 is a young member. During the evolutionary diversification of horses, the EqERV-I family diverged 1.7 Mya to 38.7 Mya. Reverse transcription quantitative real-time PCR (RT-qPCR) amplification of EqERV pol genes showed greater expression in the cerebellum of the Jeju horse than the Thoroughbred horse. These results could contribute further dynamic studies for horse genome in relation to EqERV gene function.

Molecular epidemiologic study of a human immunodeficiency virus 1 outbreak in haemophiliacs B infected through clotting factor 9 after 1990

Cho, Y. K.,Foley, B. T.,Sung, H.,Kim, Y. B.,Kim, J. H. S. Karger 2007 Vox Sanguinis Vol.92 No.2

<P>Background and Objectives </P><P>Twenty haemophiliacs were diagnosed as infected with human immunodeficiency virus 1 (HIV-1), 1 to 2 years after exposure to clotting factor 9 manufactured in Korea, beginning in early 1990. This study assessed the genetic relationships between viruses found in plasma donors and haemophiliacs.</P><P>Materials and Methods </P><P>Sequencing of the <I>nef</I> and <I>pol</I> genes of viruses from infected haemophiliacs, plasma donors whose plasma was used in domestic clotting factor manufacture, haemophiliacs infected outside Korea, and local controls were determined by nested polymerase chain reactions and direct DNA sequencing. Phylogenetic analysis was used to investigate the relationships among the sequences.</P><P>Results </P><P>Both plasma donors and the haemophiliacs were infected with a subclade of subtype B that is a founder effect lineage in Korea.</P><P>Conclusion </P><P>Our data indicate that HIV-1 transmission to 20 haemophiliacs occurred through intravenous injection of Korean-made clotting factor.</P><P>Summary </P><P>A clotting factor made in Korea from blood from cash-paid donors infected at least 20 haemophiliacs with HIV-1 subtype B.</P>