Molecular Characterization and Placental Expression of HERV-W, a New Human Endogenous Retrovirus Family

ABSTRACT The multiple sclerosis-associated retrovirus (MSRV) isolated from plasma of MS patients was found to be phylogenetically and experimentally related to human endogenous retroviruses (HERVs). To characterize the MSRV-related HERV family and to test the hypothesis of a replication-competent HERV, we have investigated the expression of MSRV-related sequences in healthy tissues. The expression of MSRV-related transcripts restricted to the placenta led to the isolation of overlapping cDNA clones from a cDNA library. These cDNAs spanned a 7.6-kb region containing gag, pol, and env genes; RU5 and U3R flanking sequences; a polypurine tract; and a primer binding site (PBS). As this PBS showed similarity to avian retrovirus PBSs used by tRNATrp, this new HERV family was named HERV-W. Several genomic elements were identified, one of them containing a complete HERV-W unit, spanning all cDNA clones. Elements of this multicopy family were not replication competent, asgag and pol open reading frames (ORFs) were interrupted by frameshifts and stop codons. A complete ORF putatively coding for an envelope protein was found both on the HERV-W DNA prototype and within an RU5-env-U3R polyadenylated cDNA clone. Placental expression of 8-, 3.1-, and 1.3-kb transcripts was observed, and a putative splicing strategy was described. The apparently tissue-restricted HERV-W long terminal repeat expression is discussed with respect to physiological and pathological contexts.

[1]  J. Mak,et al.  Primer tRNAs for reverse transcription , 1997, Journal of virology.

[2]  P. L. Le Tissier,et al.  Endogenous retroviruses and the evolution of resistance to retroviral infection. , 1997, Trends in microbiology.

[3]  B. Conrad,et al.  A Human Endogenous Retroviral Superantigen as Candidate Autoimmune Gene in Type I Diabetes , 1997, Cell.

[4]  C. Voisset,et al.  Molecular identification of a novel retrovirus repeatedly isolated from patients with multiple sclerosis. The Collaborative Research Group on Multiple Sclerosis. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[5]  C Patience,et al.  Our retroviral heritage. , 1997, Trends in genetics : TIG.

[6]  L. Villarreal,et al.  On viruses, sex, and motherhood , 1997, Journal of virology.

[7]  J. Garson,et al.  Development of a pan‐retrovirus detection system for multiple sclerosis studies , 1997, Acta neurologica Scandinavica. Supplementum.

[8]  J. Stoye,et al.  Retrotransposons, Endogenous Retroviruses, and the Evolution of Retroelements , 1997 .

[9]  C. Petropoulos.  Retroviral Taxonomy, Protein Structures, Sequences, and Genetic Maps , 1997 .

[10]  Vm Vogt.  Retroviral Virions and Genomes , 1997 .

[11]  Hughes Sh,et al.  Retrotransposons, Endogenous Retroviruses, and the Evolution of Retroelements -- Retroviruses , 1997 .

[12]  H. Varmus,et al.  Retroviral Virions and Genomes -- Retroviruses , 1997 .

[13]  Saïd Abdeddaïm.  Fast and Sound Two-Step Algorithms for Multiple Alignment of Nucleic Sequences , 1997, Int. J. Artif. Intell. Tools.

[14]  Manolo Gouy,et al.  SEAVIEW and PHYLO_WIN: two graphic tools for sequence alignment and molecular phylogeny , 1996, Comput. Appl. Biosci..

[15]  A. Dress,et al.  Multiple DNA and protein sequence alignment based on segment-to-segment comparison. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[16]  M. Palmarini,et al.  The exogenous form of Jaagsiekte retrovirus is specifically associated with a contagious lung cancer of sheep , 1996, Journal of virology.

[17]  R. Weiss,et al.  Abundance of an endogenous retroviral envelope protein in placental trophoblasts suggests a biological function. , 1995, Virology.

[18]  L. Longo,et al.  Characterization and genomic mapping of the ZNF80 locus: expression of this zinc-finger gene is driven by a solitary LTR of ERV9 endogenous retroviral family. , 1995, Nucleic acids research.

[19]  P. A. Schad,et al.  Plaque-associated expression of human herpesvirus 6 in multiple sclerosis. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[20]  D. S. Prestridge.  Predicting Pol II promoter sequences using transcription factor binding sites. , 1995, Journal of molecular biology.

[21]  B. Rost,et al.  Transmembrane helices predicted at 95% accuracy , 1995, Protein science : a publication of the Protein Society.

[22]  F. Tekaia,et al.  Isolation from human brain of six previously unreported cDNAs related to the reverse transcriptase of human endogenous retroviruses. , 1995, AIDS research and human retroviruses.

[23]  R. Kurth,et al.  Identification of a Rev-related protein by analysis of spliced transcripts of the human endogenous retroviruses HTDV/HERV-K , 1995, Journal of virology.

[24]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[25]  Erik L. L. Sonnhammer,et al.  A workbench for large-scale sequence homology analysis , 1994, Comput. Appl. Biosci..

[26]  H. Hansen,et al.  A Putative New Retrovirus Associated with Multiple Sclerosis and the Possible Involvement of Epstein‐Barr Virus in This Disease a , 1994, Annals of the New York Academy of Sciences.

[27]  D. Mager,et al.  Endogenous Human Retroviruses , 1994 .

[28]  R. Weiss,et al.  The human endogenous retrovirus ERV-3 is upregulated in differentiating placental trophoblast cells. , 1993, Virology.

[29]  R. Kurth,et al.  Evidence that HERV-K is the endogenous retrovirus sequence that codes for the human teratocarcinoma-derived retrovirus HTDV. , 1993, Virology.

[30]  Jean-Michel Claverie,et al.  Information Enhancement Methods for Large Scale Sequence Analysis , 1993, Comput. Chem..

[31]  R. Kurth,et al.  Identification of human endogenous retroviruses with complex mRNA expression and particle formation. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[32]  J. Blomberg,et al.  Sequence variation of human endogenous retrovirus ERV9-related elements in an env region corresponding to an immunosuppressive peptide: transcription in normal and neoplastic cells , 1993, Journal of virology.

[33]  M. Strazzullo,et al.  Structural and functional organization of the human endogenous retroviral ERV9 sequences. , 1992, Virology.

[34]  C. Kozak,et al.  Retroviruses in Rodents , 1992 .

[35]  C. Geny,et al.  In vitro transmission and antigenicity of a retrovirus isolated from a multiple sclerosis patient. , 1992, Research in virology.

[36]  M. Kozak.  A consideration of alternative models for the initiation of translation in eukaryotes. , 1992, Critical reviews in biochemistry and molecular biology.

[37]  J. Perret,et al.  Antibody to reverse transcriptase of human retroviruses in multiple sclerosis , 1991, Acta neurologica Scandinavica.

[38]  W. Pearson.  Searching protein sequence libraries: comparison of the sensitivity and selectivity of the Smith-Waterman and FASTA algorithms. , 1991, Genomics.

[39]  A. Simeone,et al.  Identification and characterization of novel human endogenous retroviral sequences prefentially expressed in undifferentiated embryonal carcinoma cells. , 1991, Nucleic acids research.

[40]  C. Geny,et al.  Isolation of retrovirus from patients with multiple sclerosis , 1991, The Lancet.

[41]  Dan S. Prestridge,et al.  SIGNAL SCAN: a computer program that scans DNA sequences for eukaryotic transcriptional elements , 1991, Comput. Appl. Biosci..

[42]  R. Hohlfeld,et al.  [Multiple sclerosis and retroviruses]. , 2009, Deutsche medizinische Wochenschrift.

[43]  Wen-Hsiung Li,et al.  Fundamentals of molecular evolution , 1990 .

[44]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[45]  K. Shimotohno,et al.  Human proviral mRNAs down regulated in choriocarcinoma encode a zinc finger protein related to Krüppel , 1990, Molecular and cellular biology.

[46]  L. Lania,et al.  Identification of new human repetitive sequences: characterization of the corresponding cDNAs and their expression in embryonal carcinoma cells. , 1989, Nucleic acids research.

[47]  A. Vahlne,et al.  Isolation of herpes simplex virus type 1 during first attack of multiple sclerosis , 1989, Annals of neurology.

[48]  M. Kozak.  The scanning model for translation: an update , 1989, The Journal of cell biology.

[49]  M. Rush,et al.  Detection of multiple, novel reverse transcriptase coding sequences in human nucleic acids: relation to primate retroviruses , 1989, Journal of virology.

[50]  J. Perret,et al.  Leptomeningeal cell line from multiple sclerosis with reverse transcriptase activity and viral particles. , 1989, Research in virology.

[51]  D. Lipman,et al.  Improved tools for biological sequence comparison. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[52]  E. Larsson,et al.  Absence of expression of a human endogenous retrovirus is correlated with choriocarcinoma , 1988, International journal of cancer.

[53]  M. Cohen,et al.  ERV3 Human endogenous provirus mRNAs are expressed in normal and malignant tissues and cells, but not in choriocarcinoma tumor cells , 1988, Journal of cellular biochemistry.

[54]  P. Savatier,et al.  Partial nucleotide sequence of the avian erythroblastosis virus (AEV ES4). , 1987, Nucleic acids research.

[55]  R. Ohlsson,et al.  Tissue-specific expression of human provirus ERV3 mRNA in human placenta: two of the three ERV3 mRNAs contain human cellular sequences , 1987, Journal of virology.

[56]  N. Saitou,et al.  The neighbor-joining method: a new method for reconstructing phylogenetic trees. , 1987, Molecular biology and evolution.

[57]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[58]  T. Takano,et al.  The entire nucleotide sequence of baboon endogenous virus DNA: A chimeric genome structure of murine type C and simian type D retroviruses , 1987 .

[59]  R. Snyderman,et al.  Inhibition of lymphocyte proliferation by a synthetic peptide homologous to retroviral envelope proteins. , 1985, Science.