Disease relevance of ERV3

• The human endogenous retroviruses (HERVs), ERV3 (HERV-R) and HERV-K, are both known to be transcriptionally active in human placenta [1].
• ERV3, a full-length human endogenous provirus: chromosomal localization and evolutionary relationships [2].
• Although ERV3 and lambda 4-1 expression may not be directly associated with the pathogenic pathway of RA, the possibility exists that human ERV may have a causative role in autoimmune diseases, including RA [3].
• A search in dbEST revealed ERV3 RNA expression in placenta, skin, carcinoid tumor, and adrenal glands [4].
• EXPERIMENTAL DESIGN: Reverse transcription-PCR (RT-PCR) was used to examine expression of the envelope (env) region of ERV3, HERV-E4-1, and HERV-K in breast cancer cell lines, human breast tumor samples, adjacent uninvolved breast tissues, nonmalignant breast tissues, and placenta [5].

High impact information on ERV3

• RNA transcripts of the HERV-R (ERV3) human provirus that are abundant in placenta but absent in choriocarcinoma contain nonproviral genomic sequences at their 3' ends [6].
• The expression of the envelope (env) of ERV3 at chromosome 7q11 was also studied by using stringent in situ hybridization [4].
• The ERV3 locus at chromosome 7q11 is a much studied human endogenous retroviral (HERV) sequence, owing to an env open reading frame (ORF) and placental RNA and protein expression [4].
• In addition to elements closely related to ERV3, the group included the previously known retinoic acid-inducible element, RRHERVI, also referred to as HERV15, but was separate from the related HERV-E elements [4].
• An analysis of the human genome demonstrated that ERV3 is one of a group of 41 highly related elements (ERV3-like HERVs) which use proline, isoleucine, or arginine tRNA in their primer binding sites [4].

Chemical compound and disease context of ERV3

• It appeared to be unassociated with methylation because the ERV3 provirus was similarly methylated in the DNA of placental chorionic villi and choriocarcinoma cells, and ERV3 transcription in choriocarcinoma cells was not induced by 5-azacytidine [7].

Biological context of ERV3

• DNA sequence analysis of this clone revealed that it is identical to the ERV3 genomic clone in the 1110 nucleotides that were sequenced [8].
• The ERV3 genome was determined to reside at a single locus on human chromosome 7 using a panel of rodent X human somatic cell hybrids [2].
• DNA sequencing within the clone and comparisons with other retroviruses revealed that ERV3 contains gag and pol gene sequences that are significantly related to those of mammalian type C retroviruses and previously described human endogenous proviruses [2].
• It appears that ERV3 is expressed in an organ-specific way during embryogenesis and might suggest a possible role in the development and differentiation of human tissues [1].
• A full-length human endogenous provirus termed ERV3 was isolated from a human fetal recombinant DNA library by low stringency hybridization with two probes: baboon endogenous virus LTR; and a pol-env subclone from the endogenous chimpanzee provirus, CH2 [2].

Anatomical context of ERV3

• The highest level of ERV3 env expression was detected in primitive adrenal cortex [1].
• Although the level of ERV3 expression in cultured synovial cells did not change with IL-1 beta treatment, the level for cultured proximal tubular epithelial cells (hKEC) was up-regulated [3].
• Demethylation of ERV3, an endogenous retrovirus regulating the Krüppel-related zinc finger gene H-plk, in several human cell lines arrested during early monocyte development [9].
• QPCR results for ERV3 were compatible with previously published results, with a stronger expression in adrenal gland and placenta than in 15 other human tissues [4].
• We conclude that ERV3 env is most strongly expressed in adrenal and sebaceous glands as well as in placenta [4].

Associations of ERV3 with chemical compounds

• A rabbit antiserum against synthetic peptides corresponding with the HERV-R env gene sequence led to detection of an 85 kDa product as a glycoprotein in the Harderian glands [10].
• This high-level expression of HERV-R in the adrenal cortex may possibly relate to differentiation and/or steroid production by adrenocortical cells [11].

Regulatory relationships of ERV3

• However, expression in the adrenal gland showed consistently high levels in every individual. lambda 4-1 (HERV-E) mRNA was expressed less compared with that of ERV3, and could not be detected in the adrenal gland by Northern blot, although the expression of lambda 4-1 generally correlated with that of ERV-3 in placentas [12].

Other interactions of ERV3

• The nucleotide sequence of the env gene of a previously described human provirus (ERV3) has been determined beginning near the 3'-end of the pol gene and continuing through the 3'-LTR [8].
• By Northern blot analysis using fresh synovial tissues, cultured synovial cells, and peripheral blood mononuclear cells (PBMC) from patients with RA, we noted two molecular species of ERV3 mRNAs of 3.5 kb and 9.0 kb sizes, and one single molecular species of lambda 4-1 mRNAs of 4.2 kb size [3].
• Using an enzymatic amplification technique, we found expression of the endogenous retroviral sequences, HRES-1, HERV-K10 and ERV3 in most samples of peripheral blood mononuclear cells from MS patients and controls without obvious differences between these two groups [13].
• A possible association between the endogenous retrovirus, ERV3, and multiple sclerosis (MS) was examined [14].

Analytical, diagnostic and therapeutic context of ERV3

• We determined the sequences of the HERV-R env genes obtained from the genomic DNA of primates using PCR and sequencing tools [15].
• Assignment of the endogenous retrovirus HERV-R (ERV3) to human chromosome 7q11.2 by radiation hybrid mapping [16].

References