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

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.

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Comparison of the convergent receptor utilization of a retargeted feline leukemia virus envelope with a naturally-occurring porcine endogenous retrovirus A

Virology ◽

10.1016/j.virol.2012.02.012 ◽

2012 ◽

Vol 427 (2) ◽

pp. 118-126 ◽

Cited By ~ 8

Author(s):

Peter M. Mazari ◽

Takele Argaw ◽

Leonardo Valdivieso ◽

Xia Zhang ◽

Katherine T. Marcucci ◽

...

Keyword(s):

Leukemia Virus ◽

Endogenous Retrovirus ◽

Feline Leukemia Virus ◽

Virus Envelope ◽

Porcine Endogenous Retrovirus ◽

Naturally Occurring

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A soluble envelope protein of endogenous retrovirus (FeLIX) present in serum of domestic cats mediates infection of a pathogenic variant of feline leukemia virus

Journal of General Virology ◽

10.1099/vir.0.071688-0 ◽

2015 ◽

Vol 96 (3) ◽

pp. 681-687 ◽

Cited By ~ 2

Author(s):

Shoichi Sakaguchi ◽

Takayuki Shojima ◽

Daisuke Fukui ◽

Takayuki Miyazawa

Keyword(s):

Envelope Protein ◽

Leukemia Virus ◽

Endogenous Retrovirus ◽

Pathogenic Variant ◽

Feline Leukemia Virus ◽

Domestic Cats

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

Journal of General Virology ◽

10.1099/vir.0.064857-0 ◽

2014 ◽

Vol 95 (8) ◽

pp. 1827-1831 ◽

Cited By ~ 5

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.

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

Journal of General Virology ◽

10.1099/vir.0.047399-0 ◽

2013 ◽

Vol 94 (3) ◽

pp. 643-651 ◽

Cited By ~ 15

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.

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Method to map antigenic determinants recognized by monoclonal antibodies: localization of a determinant of virus neutralization on the feline leukemia virus envelope protein gp70.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.81.12.3675 ◽

1984 ◽

Vol 81 (12) ◽

pp. 3675-3679 ◽

Cited By ~ 33

Author(s):

J. H. Nunberg ◽

G. Rodgers ◽

J. H. Gilbert ◽

R. M. Snead

Keyword(s):

Monoclonal Antibodies ◽

Envelope Protein ◽

Leukemia Virus ◽

Feline Leukemia Virus ◽

Virus Neutralization ◽

Antigenic Determinants ◽

Virus Envelope ◽

Virus Envelope Protein

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Establishing the Reactivity of Monoclonal Antibodies against Porcine Endogenous Retrovirus Envelope Protein

Intervirology ◽

10.1159/000077832 ◽

2004 ◽

Vol 47 (2) ◽

pp. 93-101 ◽

Cited By ~ 3

Author(s):

Shih-Rong Wang ◽

Jen-Ting Chang ◽

Meng-Shiue Lin ◽

Chen-Yi Chiang ◽

Hwan-You Chang

Keyword(s):

Monoclonal Antibodies ◽

Envelope Protein ◽

Endogenous Retrovirus ◽

Porcine Endogenous Retrovirus

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Identification of a Full-Length cDNA for an Endogenous Retrovirus of Miniature Swine

Journal of Virology ◽

10.1128/jvi.72.5.4503-4507.1998 ◽

1998 ◽

Vol 72 (5) ◽

pp. 4503-4507 ◽

Cited By ~ 192

Author(s):

Donna E. Akiyoshi ◽

Maria Denaro ◽

Haihong Zhu ◽

Julia L. Greenstein ◽

Papia Banerjee ◽

...

Keyword(s):

Amino Acid ◽

Leukemia Virus ◽

Endogenous Retrovirus ◽

Amino Acid Sequences ◽

Full Length ◽

Endogenous Retroviruses ◽

Miniature Swine ◽

Sequence Identity ◽

Multiple Organs ◽

Porcine Endogenous Retrovirus

ABSTRACT Endogenous retroviruses of swine are a concern in the use of pig-derived tissues for xenotransplantation into humans. The nucleotide sequence of porcine endogenous retrovirus taken from lymphocytes of miniature swine (PERV-MSL) has been characterized. PERV-MSL is a type C retrovirus of 8,132 bp with the greatest nucleic acid sequence identity to gibbon ape leukemia virus and murine leukemia virus. Constitutive production of PERV-MSL RNA has been detected in normal leukocytes and in multiple organs of swine. The copy numbers of full-length PERV sequences per genome (approximately 8 to 15) vary among swine strains. The open reading frames for gag, pol, andenv in PERV-MSL have over 99% amino acid sequence identity to those of Tsukuba-1 retrovirus and are highly homologous to those of endogenous retrovirus of cell line PK15 (PK15-ERV). Most of the differences in the predicted amino acid sequences of PK15-ERV and PERV-MSL are in the SU (cell attach- ment) region ofenv. The existence of these PERV clones will enable studies of infection by endogenous retroviruses in xenotransplantation.

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The Receptor Binding Site of Feline Leukemia Virus Surface Glycoprotein Is Distinct from the Site Involved in Virus Neutralization

Journal of Virology ◽

10.1128/jvi.72.4.3268-3277.1998 ◽

1998 ◽

Vol 72 (4) ◽

pp. 3268-3277 ◽

Cited By ~ 9

Author(s):

I. K. Ramsey ◽

N. Spibey ◽

O. Jarrett

Keyword(s):

Neutralizing Antibodies ◽

Leukemia Virus ◽

Variable Region ◽

Feline Leukemia Virus ◽

Surface Glycoprotein ◽

Cell Surface Receptor ◽

Receptor Binding Site ◽

Virus Surface ◽

Recombinant Glycoproteins

ABSTRACT The external surface glycoprotein (SU) of feline leukemia virus (FeLV) contains sites which define the viral subgroup and induce virus-neutralizing antibodies. The subgroup phenotypic determinants have been located to a small variable region, VR1, towards the amino terminus of SU. The sites which function as neutralizing epitopes in vivo are unknown. Recombinant SU proteins were produced by using baculoviruses that contained sequences encoding the SUs of FeLV subgroup A (FeLV-A), FeLV-C, and two chimeric FeLVs (FeLV-215 and FeLV-VC) in which the VR1 domain of FeLV-A had been replaced by the corresponding regions of FeLV-C isolates. The recombinant glycoproteins, designated Bgp70-A, -C, -215, and -VC, respectively, were similar to their wild-type counterparts in several immunoblots and inhibited infection of susceptible cell lines in a subgroup-specific manner. Thus, Bgp70-A interfered with infection by FeLV-A, whereas Bgp70-C, -VC, and -215 did not. Conversely, Bgp70-C, -VC, and -215 blocked infection with FeLV-C, while Bgp70-A had no effect. These results indicate that the site on SU which binds to the FeLV cell surface receptor was preserved in the recombinant glycoproteins. It was also found that the recombinant proteins were able to bind naturally occurring neutralizing antibodies. Bgp70-A, -VC, and -215 interfered with the action of anti-FeLV-A neutralizing antibodies, whereas Bgp70-C did not. Furthermore, Bgp70-C interfered with the action of anti-FeLV-C neutralizing antibodies, while the other proteins did not. These results indicate that the neutralizing epitope(s) of FeLV SU lies outside the subgroup-determining VR1 domain.

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Fusion-Defective Gibbon Ape Leukemia Virus Vectors Can Be Rescued by Homologous but Not Heterologous Soluble Envelope Proteins

Journal of Virology ◽

10.1128/jvi.76.9.4267-4274.2002 ◽

2002 ◽

Vol 76 (9) ◽

pp. 4267-4274 ◽

Cited By ~ 21

Author(s):

Karen B. Farrell ◽

Yuan-Tsang Ting ◽

Maribeth V. Eiden

Keyword(s):

Viral Entry ◽

Culture Medium ◽

Leukemia Virus ◽

Envelope Proteins ◽

Feline Leukemia Virus ◽

Receptor Binding Domain ◽

Epitope Tag ◽

Transporter Protein ◽

Gibbon Ape Leukemia Virus ◽

First Time

ABSTRACT Murine leukemia virus (MLV)-derived envelope proteins containing alterations in or adjacent to the highly conserved PHQ motif present at the N terminus of the envelope surface subunit (SU) are incorporated into vector particles but are not infectious due to a postbinding block to viral entry. These mutants can be rendered infectious by the addition of soluble receptor-binding domain (RBD) proteins in the culture medium. The RBD proteins that rescue the infectivity of these defective MLV vectors can be derived from the same MLV or from other MLVs that use distinct receptors to mediate entry. We have now constructed functional immunologically reactive gibbon ape leukemia virus (GALV) envelope proteins, tagged with a feline leukemia virus (FeLV)-derived epitope tag, which are efficiently incorporated into infectious particles. Tagged GALV envelope proteins bind specifically to cells expressing the phosphate transporter protein Pit1, demonstrating for the first time that Pit1 is the binding receptor for GALV and not a coreceptor or another type of GALV entry factor. We have also determined that GALV particles bearing SU proteins with an insertion C-terminal to the PHQ motif (GALV I10) bind Pit1 but fail to infect cells. Incubation with soluble GALV RBD renders GALV I10 particles infectious, whereas incubation with soluble RBDs from MLV or FeLV-B does not. This finding is consistent with the results obtained by Lauring et al. using FeLV-T, a virus that employs Pit1 as a receptor but requires soluble FeLV RBD for entry. MLV and GALV RBDs are not able to render FeLV-T infectious (A. S. Lauring, M. M. Anderson, and J. Overbaugh, J. Virol. 75:8888-8898, 2001). Together, these results suggest that fusion-defective FeLV-T and GALV are restricted to homologous RBD rescue of infectivity.

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