Transcriptional Control of Endogenous Virus Genes in Murine Lymphocytes

Jf, DeLamarter; Rp, Monckton; Moroni, Christoph

doi:10.1099/0022-1317-52-2-371

Cited by 3 publications

(5 citation statements)

References 10 publications

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“…The endogenous retroviruses of the rat are not well studied [22], but a strong homology with murine and feline leukemia viruses and PERV may be expected. Expression of endogenous retroviruses has been described in numerous species under physiological (e.g., immune responses [23-26]) or pathological conditions (e.g., in tumors of animals [27] and man [28]). Since in hamsters no antibodies cross-reacting with PERV proteins were found, these immunization studies could be performed.…”

Section: Discussionmentioning

confidence: 99%

Increased titers of neutralizing antibodies after immunization with both envelope proteins of the porcine endogenous retroviruses (PERVs)

Denner

Mihica

Kaulitz

et al. 2012

Virol J

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Despite enormous difficulties to induce antibodies neutralizing HIV-1, especially broadly neutralizing antibodies directed against the conserved membrane proximal external region (MPER) of the transmembrane envelope protein, such antibodies can be easily induced in the case of gammaretroviruses, among them the porcine endogenous retroviruses (PERVs). In addition to neutralizing antibodies directed against the transmembrane envelope protein p15E, neutralizing antibodies were also induced by immunization with the surface envelope protein gp70. PERVs represent a special risk for xenotransplantation using pig tissues or organs since they are integrated in the genome of all pigs and infect human cells and a vaccine may protect from transmission to the recipient. To investigate the effect of simultaneous immunization with both proteins in detail, a study was performed in hamsters. Gp70 and p15E of PERV were produced in E. coli, purified and used for immunization. All animals developed binding antibodies against the antigens used for immunization. Sera from animals immunized with p15E recognized epitopes in the MPER and the fusion peptide proximal region (FPPR) of p15E. One MPER epitope showed a sequence homology to an epitope in the MPER of gp41 of HIV-1 recognized by broadly neutralizing antibodies found in HIV infected individuals. Neutralizing antibodies were detected in all sera. Most importantly, sera from animals immunized with gp70 had a higher neutralizing activity when compared with the sera from animals immunized with p15E and sera from animals immunized with gp70 together with p15E had a higher neutralizing activity compared with sera from animals immunized with each antigen alone. These immunization studies are important for the development of vaccines against other retroviruses including the human immunodeficiency virus HIV-1.

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Section: Discussionmentioning

confidence: 99%

Increased titers of neutralizing antibodies after immunization with both envelope proteins of the porcine endogenous retroviruses (PERVs)

Denner

Mihica

Kaulitz

et al. 2012

Virol J

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“…We show for the first time that PERV release correlates with the extent of proliferation. Release of endogenous retroviruses after stimulation of immune cells has also been reported for other species, among them mice, for example after stimulation of lymphocytes with B cell mitogens [42,43], during mixed lymphocyte reactions and even in vivo, during the graft-versus-host reaction [44] and after immunisation using antigens and different adjuvants [45]. PERVs were activated by a T cell mitogen alone; in contrast, murine endogenous retroviruses could be activated only when in addition to the T cell mitogen PHA the drug bromodeoxyuridine was given [43,44].…”

Section: Discussionmentioning

confidence: 99%

“…However, this model is difficult to interpret, since the immunosuppression in these mice is not comparable with the immunosuppression expected to be used during xenotransplantation, because microchimerism due to the presence of pig cells made the interpretation difficult and because the involvement of murine endogenous retroviruses is still unknown. In mice, endogenous retroviruses are often expressed [42,43] and they may recombine or reconstitute PERV to allow infection and spread.…”

Section: Discussionmentioning

confidence: 99%

Differences in Release and Determination of Subtype of Porcine Endogenous Retroviruses Produced by Stimulated Normal Pig Blood Cells

2003

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Objective: Porcine endogenous retroviruses (PERVs) are of particular concern with xenotransplantations using pig cells, tissues or organs as they are present in the genome of all pig strains and are able to infect human cells in vitro. However, it remains unclear whether PERV particles will be produced in vivo and whether they may infect xenotransplant recipients. Since normal pig peripheral blood mononuclear cells (PBMCs) may be transmitted together with the transplanted organ, the production of PERVs by stimulated PBMCs was studied in vitro. Methods: To simulate antigen-induced activation of PBMCs, phytohaemagglutinin (PHA), a T cell mitogen, and the phorbol ester O-tetradecanoylphorbol-13-acetate (TPA), a tumour promoter, were used. Virus release was estimated by measuring reverse transcriptase (RT) activity and by RT-PCR of pelleted viruses. Results: Treatment of pig PBMCs with PHA or TPA induced the release of PERVs. For the first time, a correlation between the extent of proliferation of pig PBMCs and PERV production was shown. In addition, PERV release by non-proliferating cells and differences in virus production between stimuli as well as between different pig strains and individuals of one strain were observed. Subtype analysis revealed the release of the three subtypes PERV-A, PERV-B and PERV-C. In contrast to murine endogenous retroviruses, PERVs were induced by PHA alone. Conclusion: The data suggest that the PBMCs transmitted within a xenotransplant may release PERV. These data also suggest that pig strains producing low amounts of virus could be more suitable for xenotransplantation.

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“…In other words, retrovirus expression is a consequence of B-cell activation. LPS stimulation of cultures apparently plays an additional role in BUdR-treated cultures, that of promoting BUdR incorporation, which leads to increased retrovirus RNA synthesis (DeLamarter et al, 1981).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have implicated provirus transcription in virus expression (Besmer et al, 1975;Thomson et al, 1980;DeLamarter et al, 1981). It has been suggested that alterations in DNA methylation might provide a means of controlling gene expression (Razin & Riggs, 1980).…”

Section: Discussionmentioning

confidence: 99%

Proliferation and Differentiation Requirements for the Induction of Two Retroviral Loci during B-Cell Activation

Stoye

Moroni

1985

Journal of General Virology

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Transcriptional Control of Endogenous Virus Genes in Murine Lymphocytes

Cited by 3 publications

References 10 publications

Increased titers of neutralizing antibodies after immunization with both envelope proteins of the porcine endogenous retroviruses (PERVs)

Increased titers of neutralizing antibodies after immunization with both envelope proteins of the porcine endogenous retroviruses (PERVs)

Differences in Release and Determination of Subtype of Porcine Endogenous Retroviruses Produced by Stimulated Normal Pig Blood Cells

Proliferation and Differentiation Requirements for the Induction of Two Retroviral Loci during B-Cell Activation

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