scholarly journals Large Number of Polymorphic Nucleotides and a Termination Codon in theenvGene of the Endogenous Human Retrovirus ERV3

1998 ◽  
Vol 14 (3) ◽  
pp. 127-133 ◽  
Author(s):  
H. B. Rasmussen ◽  
J. Clausen
Keyword(s):  
Demyelinating Disease ◽  
Stop Codon ◽  
Endogenous Retrovirus ◽  
Termination Codon ◽  
Human Endogenous Retrovirus ◽  
Nucleotide Substitutions ◽  
Reading Frame ◽  
Amino Acid Code ◽  
Human Retrovirus ◽  
Autoimmune Etiology

The terminal portion of thepolgene and the entireenvgene of the human endogenous retrovirus ERV3 was screened for polymorphic nucleotides. For this purpose fragments amplified from the desired regions of ERV3 were subjected to single strand conformational analysis (SSCP analysis). Using this approach, we detected 13 polymorphic nucleotides, namely four in thepolgene and nine in theenvgene. Three of the nucleotide substitutions were synonymous (not affecting the amino acid code). One of the non-synonymous nucleotide substitutions changed an arginine codon to a termination codon. The alleles at the different polymorphic sites could be arranged into five ERV3 haplotypes, two of which were new.To evaluate the possible significance of the termination codon, which precludes expression of a putative immunoregulatory factor, we examined samples of DNA from patients with multiple sclerosis, a demyelinating disease of presumed autoimmune etiology. We did not find an association between the ERV3 allele with the termination codon and this disease.Perhaps the presence of a stop codon combined with the high number of non-synonymous nucleotide substitutions in the reading frame of theenvgene reflects absence of selective constraints during evolution. Obviously, our findings contradict the assumption that the reading frame of the ERV3envgene has been conserved throughout evolution.

scholarly journals Sequence Variability, Gene Structure, and Expression of Full-Length Human Endogenous Retrovirus H

2005 ◽  
Vol 79 (10) ◽  
pp. 6325-6337 ◽  
Author(s):  
Patric Jern ◽  
Göran O. Sperber ◽  
Göran Ahlsén ◽  
Jonas Blomberg
Keyword(s):  
Alternative Splicing ◽  
Stop Codon ◽  
Leukemia Virus ◽  
Consensus Sequence ◽  
Nucleotide Composition ◽  
Endogenous Retrovirus ◽  
Full Length ◽  
Gene Arrangement ◽  
Human Endogenous Retrovirus ◽  
Reading Frame

ABSTRACT Recently, we identified and classified 926 human endogenous retrovirus H (HERV-H)-like proviruses in the human genome. In this paper, we used the information to, in silico, reconstruct a putative ancestral HERV-H. A calculated consensus sequence was nearly open in all genes. A few manual adjustments resulted in a putative 9-kb HERV-H provirus with open reading frames (ORFs) in gag, pro, pol, and env. Long terminal repeats (LTRs) differed by 1.1%, indicating proximity to an integration event. The gag ORF was extended upstream of the normal myristylation start site. There was a long leader (including a “pre-gag” ORF) region positioned like the N terminus of murine leukemia virus (MLV) “glyco-Gag,” potentially encoding a proline- and serine-rich domain remotely similar to MLV pp12. Another ORF, starting inside the 5′ LTR, had no obvious similarity to known protein domains. Unlike other hitherto described gammaretroviruses, the reconstructed Gag had two zinc finger motifs. Alternative splicing of sequences related to the HERV-H consensus was confirmed using dbEST data. env transcripts were most prevalent in colon tumors, but also in normal testis. We found no evidence for full length env transcripts in the dbEST. HERV-H had a markedly skewed nucleotide composition, disfavoring guanine and favoring cytidine. We conclude that the HERV-H consensus shared a gene arrangement common to gammaretroviruses with gag separated by stop codon from pro-pol in the same reading frame, while env resides in another reading frame. There was also alternative splicing. HERV-H consensus yielded new insights in gammaretroviral evolution and will be useful as a model in studies on expression and function.

scholarly journals Effects of an Opal Termination Codon Preceding the nsP4 Gene Sequence in the O'Nyong-Nyong Virus Genome on Anopheles gambiae Infectivity

2006 ◽  
Vol 80 (10) ◽  
pp. 4992-4997 ◽  
Author(s):  
Kevin M. Myles ◽  
Cindy L. H. Kelly ◽  
Jeremy P. Ledermann ◽  
Ann M. Powers
Keyword(s):  
Anopheles Gambiae ◽  
De Novo ◽  
Stop Codon ◽  
Virus Genome ◽  
Termination Codon ◽  
De Novo Mutation ◽  
Nonstructural Proteins ◽  
Reading Frame ◽  
Fitness Advantage ◽  
Translational Readthrough

ABSTRACT The genomic RNA of an alphavirus encodes four different nonstructural proteins, nsP1, nsP2, nsP3, and nsP4. The polyprotein P123 is produced when translation terminates at an opal termination codon between nsP3 and nsP4. The polyprotein P1234 is produced when translational readthrough occurs or when the opal termination codon has been replaced by a sense codon in the alphavirus genome. Evolutionary pressures appear to have maintained genomic sequences encoding both a stop codon (opal) and an open reading frame (arginine) as a general feature of the O'nyong-nyong virus (ONNV) genome, indicating that both are required at some point. Alternate replication of ONNVs in both vertebrate and invertebrate hosts may determine predominance of a particular codon at this locus in the viral quasispecies. However, no systematic study has previously tested this hypothesis in whole animals. We report here the results of the first study to investigate in a natural mosquito host the functional significance of the opal stop codon in an alphavirus genome. We used a full-length cDNA clone of ONNV to construct a series of mutants in which the arginine between nsP3 and nsP4 was replaced with an opal, ochre, or amber stop codon. The presence of an opal stop codon upstream of nsP4 nearly doubled (75.5%) the infectivity of ONNV over that of virus possessing a codon for the amino acid arginine at the corresponding position (39.8%). Although the frequency with which the opal virus disseminated from the mosquito midgut did not differ significantly from that of the arginine virus on days 8 and 10, dissemination did began earlier in mosquitoes infected with the opal virus. Although a clear fitness advantage is provided to ONNV by the presence of an opal codon between nsP3 and nsP4 in Anopheles gambiae, sequence analysis of ONNV RNA extracted from mosquito bodies and heads indicated codon usage at this position corresponded with that of the virus administered in the blood meal. These results suggest that while selection of ONNV variants is occurring, de novo mutation at the position between nsP3 and nsP4 does not readily occur in the mosquito. Taken together, these results suggest that the primary fitness advantage provided to ONNV by the presence of an opal codon between nsP3 and nsP4 is related to mosquito infectivity.

scholarly journals An Envelope Glycoprotein of the Human Endogenous Retrovirus HERV-W Is Expressed in the Human Placenta and Fuses Cells Expressing the Type D Mammalian Retrovirus Receptor

2000 ◽  
Vol 74 (7) ◽  
pp. 3321-3329 ◽  
Author(s):  
Jean-Luc Blond ◽  
Dimitri Lavillette ◽  
Valérie Cheynet ◽  
Olivier Bouton ◽  
Guy Oriol ◽  
...  
Keyword(s):  
Envelope Glycoprotein ◽  
Expression Vector ◽  
Physiological Role ◽  
Endogenous Retrovirus ◽  
Open Reading Frame ◽  
Human Endogenous Retrovirus ◽  
Membrane Glycoprotein ◽  
Reading Frame ◽  
Herv Family ◽  
Type D

ABSTRACT A new human endogenous retrovirus (HERV) family, termed HERV-W, was recently described (J.-L. Blond, F. Besème, L. Duret, O. Bouton, F. Bedin, H. Perron, B. Mandrand, and F. Mallet, J. Virol. 73:1175–1185, 1999). HERV-W mRNAs were found to be specifically expressed in placenta cells, and an env cDNA containing a complete open reading frame was recovered. In cell-cell fusion assays, we demonstrate here that the product of the HERV-W env gene is a highly fusogenic membrane glycoprotein. Transfection of an HERV-W Env expression vector in a panel of cell lines derived from different species resulted in formation of syncytia in primate and pig cells upon interaction with the type D mammalian retrovirus receptor. Moreover, envelope glycoproteins encoded by HERV-W were specifically detected in placenta cells, suggesting that they may play a physiological role during pregnancy and placenta formation.

scholarly journals Comprehensive Characterization of the Human Endogenous Retrovirus HERV-K(HML-6) Group: Overview of Structure, Phylogeny, and Contribution to the Human Genome

2019 ◽  
Vol 93 (16) ◽  
Author(s):  
Maria Paola Pisano ◽  
Nicole Grandi ◽  
Marta Cadeddu ◽  
Jonas Blomberg ◽  
Enzo Tramontano
Keyword(s):  
Human Genome ◽  
Germ Line ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retrovirus ◽  
Genomic Context ◽  
Reading Frame ◽  
Normal Tissues ◽  
Small Proteins ◽  
Human Genes

ABSTRACTEight percent of the human genome is composed of human endogenous retroviruses (HERVs), remnants of ancestral germ line infections by exogenous retroviruses, which have been vertically transmitted as Mendelian characters. The HML-6 group, a member of the class II betaretrovirus-like viruses, includes several proviral loci with an increased transcriptional activity in cancer and at least two elements that are known for retaining an intact open reading frame and for encoding small proteins such as ERVK3-1, which is expressed in various healthy tissues, and HERV-K-MEL, a small Env peptide expressed in samples of cutaneous and ocular melanoma but not in normal tissues.IMPORTANCEWe reported the distribution and genetic composition of 66 HML-6 elements. We analyzed the phylogeny of the HML-6 sequences and identified two main clusters. We provided the first description of a Rec domain within theenvsequence of 23 HML-6 elements. A Rec domain was also predicted within the ERVK3-1 transcript sequence, revealing its expression in various healthy tissues. Evidence about the context of insertion and colocalization of 19 HML-6 elements with functional human genes are also reported, including the sequence 16p11.2, whose 5′ long terminal repeat overlapped the exon of one transcript variant of a cellular zinc finger upregulated and involved in hepatocellular carcinoma. The present work provides the first complete overview of the HML-6 elements in GRCh37(hg19), describing the structure, phylogeny, and genomic context of insertion of each locus. This information allows a better understanding of the genetics of one of the most expressed HERV groups in the human genome.

scholarly journals Structure and Phylogenetic Analysis of an Endogenous Retrovirus Inserted into the Human Growth Factor Gene Pleiotrophin

1998 ◽  
Vol 72 (7) ◽  
pp. 6065-6072 ◽  
Author(s):  
Anke M. Schulte ◽  
Anton Wellstein
Keyword(s):  
Rhesus Monkeys ◽  
Human Growth ◽  
Endogenous Retrovirus ◽  
Primer Binding Site ◽  
Human Endogenous Retrovirus ◽  
Long Terminal Repeats ◽  
Reading Frame ◽  
Growth Factor Gene ◽  
Trna Primer ◽  
Type C

ABSTRACT A human endogenous retrovirus-like element (HERV), flanked by long terminal repeats of 502 and 495 nucleotides is inserted into the human pleiotrophin (PTN) gene upstream of the open reading frame. Based on its Glu-tRNA primer binding site specificity and the location within the PTN gene, we named this element HERV-E.PTN. HERV-E.PTN appears to be a recombined viral element based on its high homology (70 to 86%) in distinct areas to members of two distantly related HERV type C families, HERV-E and retrovirus-like element I (RTVL-I). Furthermore, its pseudogene region is organized from 5′ to 3′ into gag-,pol-, env-, pol-,env-similar sequences. Interestingly, full-length and partial HERV-E.PTN-homologous sequences were found in the human X chromosome, the human hereditary haemochromatosis region, and the BRCA1 pseudogene. Finally, Southern analyses indicate that the HERV-E.PTN element is present in the PTN gene of humans, chimpanzees, and gorillas but not of rhesus monkeys, suggesting that genomic insertion occurred after the separation of monkeys and apes about 25 million years ago.

scholarly journals Functional Analysis of the env Open Reading Frame in Human Endogenous Retrovirus IDDMK1,222 Encoding Superantigen Activity

2000 ◽  
Vol 74 (14) ◽  
pp. 6386-6393 ◽  
Author(s):  
Matthias Lapatschek ◽  
Susanne Dürr ◽  
Roswitha Löwer ◽  
Christine Magin ◽  
Hermann Wagner ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell Lymphoma ◽  
Cell Receptor ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Open Reading Frames ◽  
Expression Vectors ◽  
Human Endogenous Retrovirus ◽  
Human Major Histocompatibility Complex ◽  
Reading Frame

ABSTRACT Mice harbor a family of endogenous retroviruses, the mouse mammary tumor viruses (MMTV), which encode superantigens. These superantigens are responsible for the deletion of T cells expressing certain Vβ chains of the T-cell receptor in the thymus. Human T cells are able to recognize MMTV-encoded superantigens presented by human major histocompatibility complex class II-positive cells. Owing to this and to the similarity of the human and murine immune systems, it was speculated that human endogenous retroviruses might also code for superantigens. Recently, it was reported that a proviral clone (IDDMK1,222) of the human endogenous retrovirus family HTDV/HERV-K encodes a superantigen. The putative superantigen gene was located within the env region of the virus. Stimulated by these findings, we amplified by PCR and cloned into eucaryotic expression vectors open reading frames (ORFs) which were identical or very similar to IDDMK1,222. When we transfected these vectors into A20 cells, a murine B-cell lymphoma, we were able to demonstrate mRNA expression and protein production. However, we did not find any evidence that the ORF stimulated human or murine T cells in a Vβ-specific fashion, the most prominent feature of superantigens.

scholarly journals Alternative Translation Initiation of Theiler’s Murine Encephalomyelitis Virus

1999 ◽  
Vol 73 (10) ◽  
pp. 8519-8526 ◽  
Author(s):  
Kenji Yamasaki ◽  
Conrad C. Weihl ◽  
Raymond P. Roos
Keyword(s):  
Translation Initiation ◽  
Demyelinating Disease ◽  
Stop Codon ◽  
Initiation Codon ◽  
Site Mutation ◽  
Entry Site ◽  
Theiler's Murine Encephalomyelitis Virus ◽  
Reading Frame ◽  
Theiler’S Murine Encephalomyelitis Virus ◽  
Encephalomyelitis Virus

ABSTRACT DA strain and other members of the TO subgroup of Theiler’s murine encephalomyelitis virus (TMEV) produce a chronic demyelinating disease in which the virus persists but has a restricted expression. We previously reported that TO subgroup strains, in addition to synthesizing the picornaviral polyprotein, use an alternative initiation codon just downstream from the polyprotein’s AUG to translate an 18-kDa protein called L* that is out of frame with the polyprotein (H. H. Chen et al., Nat. Med. 1:927–931, 1995; W. P. Kong and R. P. Roos, J. Virol. 65:3395–3399, 1991). L* is critically important for virus persistence and the induction of the demyelinating disease (Chen et al., 1995; G. D. Ghadge et al. J. Virol. 72:8605–8612, 1998). We have proposed that variations in the amount of translation initiation from the L* AUG versus the polyprotein AUG may occur in different cell types and therefore affect the degree of expression of viral capsid proteins. We now demonstrate that ribosomal translation initiation at the polyprotein’s initiation codon affects initiation at the L* AUG, suggesting that ribosomes land at the polyprotein’s initiation codon before scanning downstream and initiating at the L* AUG. We also find that the viral 5′ untranslated region affects utilization of the L* AUG. Surprisingly, mutant DA cDNAs were found to be infectious despite the presence of mutations of the polyprotein initiation codon or placement of a stop codon upstream of the L* AUG in the polyprotein’s reading frame. Sequencing studies showed that these viruses had a second site mutation, converting the reading frame of L* into the polyprotein’s reading frame; the results suggest that translation of the polyprotein during infection of these mutant viruses can be initiated at the L* AUG. These data are important in our understanding of translation initiation of TMEV and other RNAs that contain an internal ribosome entry site.

scholarly journals Physiological Knockout of the Envelope Gene of the Single-Copy ERV-3 Human Endogenous Retrovirus in a Fraction of the Caucasian Population

1998 ◽  
Vol 72 (4) ◽  
pp. 3442-3445 ◽  
Author(s):  
Nathalie de Parseval ◽  
Thierry Heidmann
Keyword(s):  
Stop Codon ◽  
Single Copy ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Envelope Gene ◽  
Sequence Variability ◽  
Homozygous State ◽  
Evolutionarily Conserved ◽  
Essential Function ◽  
Conserved Gene

ABSTRACT ERV-3 is an evolutionarily conserved single-copy human endogenous retrovirus with a coding envelope gene potentially involved in important placental functions. We have investigated the sequence variability of this gene among 150 unrelated Caucasian individuals and found eight polymorphic sites. One of them corresponds to the introduction of a stop codon resulting in the production of a severely truncated ERV-3 envelope protein lacking both the fusion peptide and the immunosuppressive domain of the protein. The stop codon is observed in a homozygous state in approximately 1% of Caucasian individuals without evidence for counterselection, thus precluding the involvement of any essential function of the gene in placental implantation and development. This natural knockout provides a mean to investigate other potential roles for this otherwise highly conserved gene.

scholarly journals HERV-Derived Ervpb1 Is Conserved in Simiiformes, Exhibiting Expression in Hematopoietic Cell Lineages Including Macrophages

2021 ◽  
Vol 22 (9) ◽  
pp. 4504
Author(s):  
Ayumi Matsuzawa ◽  
Jiyoung Lee ◽  
So Nakagawa ◽  
Johbu Itoh ◽  
Mahoko Takahashi Ueda ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Ex Vivo ◽  
Cell Lineage ◽  
Endogenous Retrovirus ◽  
Hematopoietic Cell ◽  
Human Endogenous Retrovirus ◽  
New World Monkeys ◽  
Reading Frame ◽  
Cell Lineages ◽  
Induced Pluripotent

(1) Background: The ERVPb1 gene in humans is derived from an envelope (Env) gene of a human endogenous retrovirus group, HERV-P(b). The ERVPb1 gene reportedly has a conserved open reading frame (ORF) in Old World monkeys. Although its forced expression led to cell-fusion in an ex vivo cell culture system, like other Env-derived genes such as syncytin-1 and -2, its mRNA expression is not placenta-specific, but almost ubiquitous, albeit being quite low in human tissues and organs, implying a distinct role for ERVPb1. (2) Methods: To elucidate the cell lineage(s) in which the ERVPb1 protein is translated in human development, we developed a novel, highly sensitive system for detecting HERV-derived proteins/peptides expressed in the tissue differentiation process of human induced pluripotent stem cells (iPSCs). (3) Results: We first determined that ERVPb1 is also conserved in New World monkeys. Then, we showed that the ERVPb1 protein is translated from a uniquely spliced ERVPb1 transcript in hematopoietic cell lineages, including a subset of macrophages, and further showed that its mRNA expression is upregulated by lipopolysaccharide (LPS) stimulation in primary human monocytes. (4) Conclusions: ERVPb1 is unique to Simiiformes and actually translated in hematopoietic cell lineages, including a subset of macrophages.

scholarly journals A Human Endogenous Retrovirus Suppresses Translation of an Associated Fusion Transcript, PLA2L

1998 ◽  
Vol 72 (7) ◽  
pp. 6164-6168 ◽  
Author(s):  
Paul E. Kowalski ◽  
Dixie L. Mager
Keyword(s):  
Cell Lines ◽  
Fusion Transcript ◽  
Endogenous Retrovirus ◽  
Full Length ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retrovirus ◽  
Stem Loop ◽  
Teratocarcinoma Cell ◽  
Reading Frame ◽  
High Level

ABSTRACT Human endogenous retroviruses (HERVs) are repetitive, noninfectious chromosomal elements degenerated from exogenous retroviruses. The HERV-H family is composed of approximately 1,000 elements which are dispersed throughout the human genome. We have shown previously that an HERV-H element splices into a downstream locus, termed PLA2L, which has a large open reading frame (ORF) containing two domains with phospholipase A2 homology. Over half of the putative 5′ untranslated region (5′ UTR) of the resulting fusion transcript is derived from HERV-H long-terminal-repeat and internal sequences. As 5′ UTRs are known to modulate translation initiation, we tested for possible effects upon gene expression at the translation level due to the 5′ fusion with HERV-H sequences. No PLA2L protein was detected in teratocarcinoma cell lines in which PLA2L mRNA is abundantly expressed. In addition, despite a high level of transcription, no protein synthesis was detected when the full-length PLA2L cDNA was expressed in COS cells. Upon removal of the 5′-terminal HERV-H sequences, PLA2L protein was seen in transfectants. The 5′ UTR contains both small ORFs and a strong predicted RNA secondary structure, both of which have been shown to contribute to translation suppression. The HERV-H sequences, combined with a unique PLA2L 5′ UTR sequence, form a predicted RNA stem-loop that has a stability greater than that proposed to negatively affect translation. Interestingly, this stem-loop is abolished when the HERV-H sequences are removed. We hypothesize that the PLA2L 5′ HERV-H sequences function as an abnormally long and complex 5′ UTR, resulting in suppression of translation in both teratocarcinoma cell lines and full-length cDNA transfectants. This is the first known example of a endogenous retrovirus integration affecting expression of a heterologous human gene at the translational level.

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