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The solitary long terminal repeats of ERV-9 endogenous retrovirus are conserved during primate evolution and possess enhancer activities in embryonic and hematopoietic cells.

ABSTRACT: The solitary long terminal repeats (LTRs) of ERV-9 endogenous retrovirus contain the U3, R, and U5 regions but no internal viral genes. They are middle repetitive DNAs present at 2,000 to 4,000 copies in primate genomes. Sequence analyses of the 5" boundary area of the erythroid beta-globin locus control region (beta-LCR) and the intron of the embryonic axin gene show that a solitary ERV-9 LTR has been stably integrated in the respective loci for at least 15 million years in the higher primates from orangutan to human. Functional studies utilizing the green fluorescent protein (GFP) gene as the reporter in transfection experiments show that the U3 region of the LTRs possesses strong enhancer activity in embryonic cells of widely different tissue origins and in adult cells of blood lineages. In both the genomic LTRs of embryonic placental cells and erythroid K562 cells and transfected LTRs of recombinant GFP plasmids in K562 cells, the U3 enhancer activates synthesis of RNAs that are initiated from a specific site 25 bases downstream of the AATAAA (TATA) motif in the U3 promoter. A second AATAAA motif in the R region does not serve as the TATA box or as the polyadenylation signal. The LTR-initiated RNAs extend through the R and U5 regions into the downstream genomic DNA. The results suggest that the ERV-9 LTR-initiated transcription process may modulate transcription of the associated gene loci in embryonic and hematopoietic cells.

SUBMITTER: Ling J

PROVIDER: S-EPMC153808 | biostudies-other | 2002 Mar

REPOSITORIES: biostudies-other

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The solitary long terminal repeats of ERV-9 endogenous retrovirus are conserved during primate evolution and possess enhancer activities in embryonic and hematopoietic cells.

Ling Jianhua J Pi Wenhu W Bollag Roni R Zeng Shan S Keskintepe Meral M Saliman Hatem H Krantz Sanford S Whitney Barry B Tuan Dorothy D

Journal of virology 20020301 5

The solitary long terminal repeats (LTRs) of ERV-9 endogenous retrovirus contain the U3, R, and U5 regions but no internal viral genes. They are middle repetitive DNAs present at 2,000 to 4,000 copies in primate genomes. Sequence analyses of the 5" boundary area of the erythroid beta-globin locus control region (beta-LCR) and the intron of the embryonic axin gene show that a solitary ERV-9 LTR has been stably integrated in the respective loci for at least 15 million years in the higher primates ...[more]

PMID: 11836419

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Project description:The risk of xenozoonosis mainly by porcine endogenous retrovirus (PERV) has been considered as one of the main hurdles in xenotransplantation and therefore should be elucidated prior to the clinical use of porcine corneal grafts. Accordingly, an investigation was performed to analyze the infectivity of PERVs from porcine keratocytes to human cells, and the long-term risk of transmission of PERVs was determined using pig-to-non-human primate (NHP) corneal transplantation models.The infectivity of PERVs from the SNU miniature pig keratocytes was investigated by coculture with a human embryonic kidney cell line. Twenty-two rhesus macaques underwent xenocorneal transplantation as follows: (i) group 1 (n=4): anterior lamellar keratoplasty (LKP) with freshly preserved porcine corneas, (ii) group 2 (n=5): anterior LKP with decellularized porcine corneas followed by penetrating keratoplasty (PKP) with allografts, (iii) group 3 (n=3): PKP under steroid-based immunosuppression, (iv) group 4 (n=4): PKP under anti-CD154 antibody-based immunosuppression, (v) group 5 (n=4): deep anterior LKP with freshly preserved porcine corneas under anti-CD40 antibody-based immunosuppression, and (vi) group 6 (n=2): PKP under anti-CD40 antibody-based immunosuppression. Postoperative blood samples were serially collected, and tissue samples were obtained from thirteen different organs at the end of each experiment. The existence of PERV DNA and RNA was investigated using PCR and RT-PCR.Using two independent in vitro infectivity tests, neither PERV pol nor pig mitochondrial cytochrome oxidase II was detected after 41 and 92 days of coculture, respectively. After xenocorneal transplantation, a total of 257 serial peripheral blood mononuclear cell samples, 34 serial plasma samples, and 282 tissue samples were obtained from the NHP recipients up to 1176 days post-transplantation. No PERV transmission was evident in any samples.Within the limits of this study, there is no evidence to support any risk of PERV transmission from porcine corneal tissues to NHP recipients, despite the existence of PERV-expressing cells in porcine corneas.

Dataset Information

The solitary long terminal repeats of ERV-9 endogenous retrovirus are conserved during primate evolution and possess enhancer activities in embryonic and hematopoietic cells.

Publications

The solitary long terminal repeats of ERV-9 endogenous retrovirus are conserved during primate evolution and possess enhancer activities in embryonic and hematopoietic cells.

Similar Datasets

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