Pseudotyping of Porcine Endogenous Retrovirus by Xenotropic Murine Leukemia Virus in a Pig Islet Xenotransplantation Model

Martina, Yuri; Kurian, Sunil M.; Cherqui, Stéphanie; Evanoff, Gabriel; Wilson, Carolyn A.; Salomon, Daniel R.

doi:10.1111/j.1600-6143.2005.00978.x

Cited by 38 publications

(29 citation statements)

References 53 publications

(81 reference statements)

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“…This agrees with data showing that mouse cells could not be infected in vitro (297,318,343), and infection experiments using high-titer PERV in vivo were negative (143). Reports claiming infection of mice with PERV (48,64,332) were based on pseudotyping of PERV with murine endogenous retroviruses (199,355). Mice transgenic for HuPAR-1 were generated, and it was reported that they could be infected with PERV in vivo (200).…”

Section: Pervssupporting

confidence: 75%

“…Interestingly, a transient infection was observed in guinea pigs (7). Reports on PERV infection of SCID mice (64,332) and athymic mice (48) represented an artifact of the mouse model: PERV infection of murine cells was the result of pseudotyping with endogenous murine retroviruses (199,355). These data closely correlate with the absence of a functional PERV receptor on mouse cells (101) and the absence of infection in other mouse models (143,165).…”

Section: Pervssupporting

confidence: 68%

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Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses

2012

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SUMMARY Xenotransplantation may be a solution to overcome the shortage of organs for the treatment of patients with organ failure, but it may be associated with the transmission of porcine microorganisms and the development of xenozoonoses. Whereas most microorganisms may be eliminated by pathogen-free breeding of the donor animals, porcine endogenous retroviruses (PERVs) cannot be eliminated, since these are integrated into the genomes of all pigs. Human-tropic PERV-A and -B are present in all pigs and are able to infect human cells. Infection of ecotropic PERV-C is limited to pig cells. PERVs may adapt to host cells by varying the number of LTR-binding transcription factor binding sites. Like all retroviruses, they may induce tumors and/or immunodeficiencies. To date, all experimental, preclinical, and clinical xenotransplantations using pig cells, tissues, and organs have not shown transmission of PERV. Highly sensitive and specific methods have been developed to analyze the PERV status of donor pigs and to monitor recipients for PERV infection. Strategies have been developed to prevent PERV transmission, including selection of PERV-C-negative, low-producer pigs, generation of an effective vaccine, selection of effective antiretrovirals, and generation of animals transgenic for a PERV-specific short hairpin RNA inhibiting PERV expression by RNA interference.

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Section: Pervssupporting

confidence: 75%

Section: Pervssupporting

confidence: 68%

Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses

2012

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“…The investigators demonstrated that the appearance of PERV positive human cells was most likely due to pseudotyping of PERV C by xenotropic murine leukemia virus, rather than authentic infection by human-tropic PERV (Yang, Wood et al 2004),. These observations were later confirmed by in vitro studies performed by Martina, et al (Martina, Kurian et al 2005). …”

Section: Animal Modelssupporting

confidence: 77%

Methods and Tools for Detection and Evaluation of the Risks of Porcine Endogenous Retrovirus in Porcine to Human Xenotransplantation

Argaw¹,

Wilson²

2012

Xenotransplantation

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“…Most promising were a series of studies with chimeric immunodeficient mice having human and pig cell transplants that consistently demonstrated PERV transmission to the human cells (11,(36)(37)(38)64). However, the conclusion that transmission of PERV to human cells was directly due to xenotransplantation must be reconsidered in light of new data demonstrating that xenotropic murine leukemia virus (X-MuLV) pseudotypes PERV and is detected where human cells are positive for PERV (36,64). These findings complicate the interpretation of results from the chimeric mouse-human-pig models, making them unsuitable for evaluation of PERV in vivo.…”

mentioning

confidence: 99%

Mice Transgenic for a Human Porcine Endogenous Retrovirus Receptor Are Susceptible to Productive Viral Infection

Martina

Marcucci

Cherqui

et al. 2006

J Virol

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Porcine endogenous retrovirus (PERV) is considered one of the major risks in xenotransplantation. No valid animal model has been established to evaluate the risks associated with PERV transmission to human patients by pig tissue xenotransplantation or to study the potential pathogenesis associated with PERV infection. In previous work we isolated two genes encoding functional human PERV receptors and proved that introduction of these into mouse fibroblasts allowed the normally nonpermissive mouse cells to become productively infected (T. A. Ericsson, Y. Takeuchi, C. Templin, G. Quinn, S. F. Farhadian, J. C. Wood, B. A. Oldmixon, K. M. Suling, J. K. Ishii, Y. Kitagawa, T. Miyazawa, D. R. Salomon, R. A. Weiss, and C. Patience, Proc. Natl. Acad. Sci. USA 100:6759-6764, 2003). In the present study we created mice transgenic for human PERV-A receptor 2 (HuPAR-2). After inoculation of transgenic animals with infectious PERV supernatants, viral DNA and RNA were detected at multiple time points, indicating productive replication. This establishes the role of HuPAR-2 in PERV infection in vivo; in addition, these transgenic mice represent a new model for determining the risk of PERV transmission and potential pathogenesis. These mice also create a unique opportunity to study the immune response to PERV infection and test potential therapeutic or preventative modalities.

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Pseudotyping of Porcine Endogenous Retrovirus by Xenotropic Murine Leukemia Virus in a Pig Islet Xenotransplantation Model

Abstract: The potential of porcine endogenous retrovirus (PERV) as a human pathogen, particularly as a public health risk, is a major concern for xenotransplantation.

Cited by 38 publications

References 53 publications

Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses

Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses

Methods and Tools for Detection and Evaluation of the Risks of Porcine Endogenous Retrovirus in Porcine to Human Xenotransplantation

Mice Transgenic for a Human Porcine Endogenous Retrovirus Receptor Are Susceptible to Productive Viral Infection

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