scholarly journals Lack of antibody response in pigs immunized with the transmembrane envelope protein of porcine endogenous retroviruses

2014 ◽  
Vol 95 (8) ◽  
pp. 1827-1831 ◽  
Author(s):  
Martina Keller ◽  
Björn Petersen ◽  
Heiner Niemann ◽  
Joachim Denner
Keyword(s):  
Neutralizing Antibodies ◽  
Mammalian Species ◽  
Neutralization Assay ◽  
Endogenous Retrovirus ◽  
Proximal Region ◽  
Endogenous Retroviruses ◽  
Placental Development ◽  
Porcine Endogenous Retrovirus ◽  
Porcine Endogenous Retroviruses ◽  
Protein P15e

Recently, we immunized different mammalian species (goats, mice, rats, rabbits, guinea pigs and hamsters) with the recombinant ectodomain of the transmembrane envelope (TM) protein p15E of porcine endogenous retrovirus (PERV). In all cases, neutralizing immune sera were induced, which recognized epitopes in the fusion peptide proximal region and the membrane proximal external region of p15E. In order to analyse whether pigs are also able to produce such antibodies, and whether such antibodies can be used to study the involvement of the TM protein in placental development (as was shown for endogenous retroviruses of other species), German landrace pigs were immunized with PERV p15E. No binding and neutralizing antibodies were produced as shown in three Western blot analyses and in a neutralization assay, indicating that pigs are tolerant to their endogenous retroviruses, at least for the ectodomain of the TM protein.

scholarly journals Identification of Novel Porcine Endogenous Betaretrovirus Sequences in Miniature Swine

2001 ◽  
Vol 75 (6) ◽  
pp. 2765-2770 ◽  
Author(s):  
Thomas Ericsson ◽  
Beth Oldmixon ◽  
Jonas Blomberg ◽  
Margaret Rosa ◽  
Clive Patience ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Fetal Liver ◽  
Phylogenetic Analyses ◽  
Mammalian Species ◽  
Peripheral Blood Lymphocytes ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Miniature Swine ◽  
Porcine Endogenous Retrovirus

ABSTRACT PCR amplification of genomic DNA from miniature swine peripheral blood lymphocytes, using primers corresponding to highly conserved regions of the polymerase (pol) gene, allowed the identification of two novel porcine endogenous retrovirus (PERV) sequences, PMSN-1 and PMSN-4. Phylogenetic analyses of the nucleotide sequences of PMSN-1 and PMSN-4 revealed them to be most closely related to betaretroviruses. The identification of PERVs belonging to theBetaretrovirus genus shows that endogenous retroviruses of this family are more broadly represented in mammalian species than previously appreciated. Both sequences contained inactivating mutations, implying that these particular loci are defective. However, Southern blot analysis showed additional copies of closely related proviruses in the miniature swine genome. Analyses of fetal and adult miniature swine tissues revealed a broad mRNA expression pattern of both PMSN-1 and PMSN-4. The most abundant expression was detected in whole bone marrow c-kit +(CD117+) progenitor bone marrow cells, fetal liver, salivary gland, and thymus. It appears unlikely that functional loci encoding these novel PERV sequences exist, but this remains to be established. The betaretrovirus sequences described in this report will allow such investigations to be actively pursued.

scholarly journals Isolation and Characterization of an Infectious Replication-Competent Molecular Clone of Ecotropic Porcine Endogenous Retrovirus Class C

2006 ◽  
Vol 80 (20) ◽  
pp. 10258-10261 ◽  
Author(s):  
Thomas Preuss ◽  
Nicole Fischer ◽  
Klaus Boller ◽  
Ralf R. Tönjes
Keyword(s):  
T Cells ◽  
Genomic Library ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Miniature Swine ◽  
Infectious Risk ◽  
Isolation And Characterization ◽  
Porcine Endogenous Retrovirus ◽  
Porcine Endogenous Retroviruses

ABSTRACT Xenotransplantation of pig organs is complicated by the existence of polytropic replication-competent porcine endogenous retroviruses (PERV) capable of infecting human cells. The potential for recombination between ecotropic PERV-C and human-tropic PERV-A and PERV-B adds another level of infectious risk. Proviral PERV-C were characterized in MAX-T cells derived from d/d haplotype miniature swine. Three proviruses were cloned from a genomic library. Clone PERV-C(1312) generated infectious particles after transfection into porcine ST-IOWA cells. Electron microscopy revealed the same morphologies of virions in MAX-T cells and in ST-IOWA cells infected with cell-free PERV-C(1312) particles, indicating that MAX-T cells harbor one functional PERV-C provirus.

scholarly journals Relative Age of Proviral Porcine Endogenous Retrovirus Sequences in Sus scrofa Based on the Molecular Clock Hypothesis

2003 ◽  
Vol 77 (22) ◽  
pp. 12363-12368 ◽  
Author(s):  
Ralf R. Tönjes ◽  
Marcus Niebert
Keyword(s):  
Sus Scrofa ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Relative Age ◽  
Repeat Structure ◽  
Porcine Endogenous Retrovirus ◽  
Porcine Endogenous Retroviruses ◽  
Different Types ◽  
Pecari Tajacu ◽  
Recent Origin

ABSTRACT Porcine endogenous retroviruses (PERV) are discussed as putative infectious agents in xenotransplantation. PERV classes A, B, and C harbor different envelope proteins. Two different types of long terminal repeat (LTR) structures exist, of which both are present only in PERV-A. One type of LTR contains a distinct repeat structure in U3, while the other is repeatless, conferring a lower level of transcriptional activity. Since the different LTR structures are distributed unequally among the proviruses and, apparently, PERV is the only virus harboring two different LTR structures, we were interested in determining which LTR is the ancestor. Replication-competent viruses can still be found today, suggesting an evolutionary recent origin. Our studies revealed that the age of PERV is at most 7.6 × 106 years, whereas the repeatless LTR type evolved approximately 3.4 × 106 years ago, being the phylogenetically younger structure. The age determined for PERV correlates with the time of separation between pigs (Suidae, Sus scrofa) and their closest relatives, American-born peccaries (Tayassuidae, Pecari tajacu), 7.4 × 106 years ago.

scholarly journals Genotyping of Porcine Endogenous Retroviruses from a Family of Miniature Swine

2004 ◽  
Vol 78 (1) ◽  
pp. 314-319 ◽  
Author(s):  
Gary Quinn ◽  
James Wood ◽  
Kristen Suling ◽  
Scott Arn ◽  
David H. Sachs ◽  
...  
Keyword(s):  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Target Cells ◽  
Nucleotide Polymorphisms ◽  
Miniature Swine ◽  
Porcine Endogenous Retrovirus ◽  
Porcine Endogenous Retroviruses ◽  
The Family ◽  
Transcript Profiles

ABSTRACT The identification of animals in an inbred miniature swine herd that consistently fail to produce replication- competent humantropic porcine endogenous retrovirus (PERV) has prompted studies on the biology of PERV in transmitter and nontransmitter animals. We analyzed PERV RNA transcript profiles in a family of inbred miniature swine (SLAd/d haplotype) in which individual members differed in their capacity to generate humantropic and ecotropic (i.e., pigtropic) virus. We identified unique HaeIII and HpaII gag restriction fragment length polymorphism (RFLP) profiles resulting from single nucleotide polymorphisms in blood cells; these were found only in animals that produced humantropic PERV. These HaeIII and HpaII gag RFLP profiles proved to be components of humantropic PERV as they were transmitted to 293 human target cells in vitro. The humantropic HaeIII and HpaII gag RFLP genotypes in the family of study were not present in other miniature swine in the herd that produced humantropic PERV, indicating that these RFLP profiles relate specifically to this family's lineage.

scholarly journals Characterization of Porcine Endogenous Retrovirus Clones from the NIH Miniature Pig BAC Library

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Seong-Lan Yu ◽  
Woo-Young Jung ◽  
Kie-Chul Jung ◽  
In-Cheol Cho ◽  
Hyun-Tae Lim ◽  
...  
Keyword(s):  
Bac Library ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Miniature Pig ◽  
Reading Frame ◽  
Porcine Endogenous Retrovirus ◽  
Open Reading Frame Length ◽  
Porcine Endogenous Retroviruses ◽  
Integration Sites

Pigs have been considered as donors for xenotransplantation in the replacement of human organs and tissues. However, porcine endogenous retroviruses (PERVs) might transmit new infectious disease to humans during xenotransplantation. To investigate PERV integration sites, 45 PERV-positive BAC clones, including 12 PERV-A, 16 PERV-B, and 17 PERV-C clones, were identified from the NIH miniature pig BAC library. The analysis of 12 selected full-length sequences of PERVs, including the long terminal repeat (LTR) region, identified the expected of open reading frame length, an indicative of active PERV, in all five PERV-C clones and one of the four PERV-B clones. Premature stop codons were observed in only three PERV-A clones. Also, eleven PERV integration sites were mapped using a 5000-rad IMpRH panel. The map locations of PERV-C clones have not been reported before, thus they are novel PERV clones identified in this study. The results could provide basic information for the elimination of site-specific PERVs in selection of pigs for xenotransplantation.

scholarly journals Porcine Endogenous Retrovirus Transmission Characteristics of an Inbred Herd of Miniature Swine

2002 ◽  
Vol 76 (6) ◽  
pp. 3045-3048 ◽  
Author(s):  
Beth A. Oldmixon ◽  
James C. Wood ◽  
Thomas A. Ericsson ◽  
Carolyn A. Wilson ◽  
Mary E. White-Scharf ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Receptor Binding Domain ◽  
Transmission Characteristics ◽  
Miniature Swine ◽  
Recombinant Viruses ◽  
Porcine Endogenous Retrovirus ◽  
Porcine Endogenous Retroviruses

ABSTRACT Here we report the identification of inbred miniature swine that failed to produce human-tropic replication-competent porcine endogenous retroviruses (HTRC PERVs), using in vitro coculture assays. When HTRC PERVs were isolated from transmitting animals, all were recombinant viruses, with the receptor-binding domain of PERV-A combining with PERV-C-related sequences.

scholarly journals Vaccination against the Koala Retrovirus (KoRV): Problems and Strategies

Animals ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 3555
Author(s):  
Joachim Denner
Keyword(s):  
Envelope Protein ◽  
Neutralizing Antibodies ◽  
Leukemia Virus ◽  
Endogenous Retrovirus ◽  
Envelope Proteins ◽  
Proximal Region ◽  
Feline Leukemia Virus ◽  
The North ◽  
Porcine Endogenous Retrovirus ◽  
Koala Retrovirus

The koala retrovirus (KoRV) is spreading in the koala population from the north to the south of Australia and is also in the process of endogenization into the koala genome. Virus infection is associated with tumorigenesis and immunodeficiency and is contributing to the decline of the animal population. Antibody production is an excellent marker of retrovirus infection; however, animals carrying endogenous KoRV are tolerant. Therefore, the therapeutic immunization of animals carrying endogenous KoRV seems to be ineffective. Using the recombinant transmembrane (TM) envelope protein of the KoRV, we immunized goats, rats and mice, obtaining in all cases neutralizing antibodies which recognize epitopes in the fusion peptide proximal region (FPPR), and in the membrane-proximal external region (MPER). Immunizing several animal species with the corresponding TM envelope protein of the closely related porcine endogenous retrovirus (PERV), as well as the feline leukemia virus (FeLV), we also induced neutralizing antibodies with similar epitopes. Immunizing with the TM envelope protein in addition to the surface envelope proteins of all three viruses resulted in higher titers of neutralizing antibodies. Immunizing KoRV-negative koalas with our vaccine (which is composed of both envelope proteins) may protect these animals from infection, and these may be the starting points of a virus-free population.

scholarly journals Identification of a novel type C porcine endogenous retrovirus: evidence that copy number of endogenous retroviruses increases during host inbreeding

2001 ◽  
Vol 82 (8) ◽  
pp. 1829-1834 ◽  
Author(s):  
Rui Mang ◽  
Jolanda Maas ◽  
Xianghong Chen ◽  
Jaap Goudsmit ◽  
Antoinette C. van der Kuyl
Keyword(s):  
Wild Boar ◽  
Copy Number ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retrovirus ◽  
Porcine Endogenous Retrovirus ◽  
Porcine Endogenous Retroviruses ◽  
Pig Genome ◽  
Multiple Copies ◽  
Type C

Different classes of porcine endogenous retroviruses (PERVs), which have the potential to infect humans during xenotransplantation, have been isolated from the pig genome. Because vertebrate genomes may contain numerous endogenous retrovirus sequences, the pig genome was examined for additional endogenous retroviruses, resulting in the isolation of a novel, complete endogenous retrovirus genome, designated PERV-E. The gag, pol and env genes of PERV-E are closely related to those of human endogenous retrovirus (HERV) 4-1, which belongs to the HERV-E family. Results of studies to determine the presence and copy number of PERVs demonstrated that PERV-E and PERV-A/B-like proviruses were present in all genomes tested, but that PERV-C was not found in two of the species examined, including wild boar. Multiple copies of PERVs could be found in each pig genome. Among all of the pig genomes tested, the wild boar genome had the lowest copy number of all PERVs, suggesting that the number of integrations of complete endogenous retroviruses is increased by inbreeding.

scholarly journals Neutralization of porcine endogenous retrovirus by antibodies against the membrane-proximal external region of the transmembrane envelope protein

2013 ◽  
Vol 94 (3) ◽  
pp. 643-651 ◽  
Author(s):  
Alexander Waechter ◽  
Magdalena Eschricht ◽  
Joachim Denner
Keyword(s):  
Neutralizing Antibodies ◽  
Endogenous Retrovirus ◽  
Immune Serum ◽  
Proximal Region ◽  
External Region ◽  
Membrane Proximal External Region ◽  
Porcine Endogenous Retrovirus ◽  
Protein Gp41 ◽  
First Time ◽  
Hiv 1

Immunization of different species including goats, rats, hamsters and guinea pigs with the recombinant ectodomain of the transmembrane envelope (TM) protein p15E of porcine endogenous retrovirus (PERV) has been shown to result in the production of virus-neutralizing antibodies. The sera recognize two groups of epitopes, one located in the fusion peptide-proximal region (FPPR) and the second in the membrane-proximal external region (MPER) of p15E. Most interestingly, the epitopes in the MPER are similar to epitopes in the TM protein gp41 of human immunodeficiency virus type 1 (HIV-1) recognized by mAbs 2F5 and 4E10, which broadly neutralize HIV-1. To study which epitope and which antibody population are involved in the process of neutralization of PERV, this study generated a new antiserum in a goat using an elongated ectodomain of p15E. The immune serum neutralized PERV at a higher titre and recognized broader epitopes in the FPPR and MPER of p15E. For the first time, antibody subpopulations were isolated from this serum using affinity chromatography with immobilized proteins and peptides corresponding to the FPPR and MPER of p15E. Only the affinity-purified antibodies specifically binding the MPER neutralized PERV, indicating that, as in the case of HIV-1, the MPER is an important target of neutralizing activity.

scholarly journals Cross-species transmission and differential fate of an endogenous retrovirus in three mammal lineages

2015 ◽  
Author(s):  
Xiaoyu Zhuo ◽  
Cedric Feschotte
Keyword(s):  
Mammalian Species ◽  
Extended Period ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Myotis Lucifugus ◽  
Multiple Infection ◽  
Deep Time ◽  
Genome Sequence Database ◽  
Species Specific ◽  
Retroviral Infections

Endogenous retroviruses (ERVs) arise from retroviruses chromosomally integrated in the host germline. ERVs are common in vertebrate genomes and provide a valuable fossil record of past retroviral infections to investigate the biology and evolution of retroviruses over a deep time scale, including cross-species transmission events. Here we took advantage of a catalog of ERVs we recently produced for the bat Myotis lucifugus to seek evidence for infiltration of these retroviruses in other mammalian species (>100) currently represented in the genome sequence database. We provide multiple lines of evidence for the cross-ordinal transmission of a gammaretrovirus endogenized independently in the lineages of vespertilionid bats, felid cats and pangolin ~13-25 million years ago. Following its initial introduction, the ERV amplified extensively in parallel in both bat and cat lineages, generating hundreds of species-specific insertions throughout evolution. However, despite being derived from the same viral species, phylogenetic and selection analyses suggest that the ERV experienced different amplification dynamics in the two mammalian lineages. In the cat lineage, the ERV appears to have expanded primarily by retrotransposition of a single proviral progenitor that lost infectious capacity shortly after endogenization. In the bat lineage, the ERV followed a more complex path of germline invasion characterized by both retrotransposition and multiple infection events. The results also suggest that some of the bat ERVs have maintained infectious capacity for extended period of time and may be still infectious today. This study provides one of the most rigorously documented cases of cross-ordinal transmission of a mammalian retrovirus. It also illustrates how the same retrovirus species has transitioned multiple times from an infectious pathogen to a genomic parasite (i.e. retrotransposon), yet experiencing different invasion dynamics in different mammalian hosts.

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