Abstract

Humanized pigs have been developed to reduce the incidence of immune rejection in xenotransplantation, but significant concerns remain, such as transmission of viral zoonosis. Porcine endogenous retroviruses (PERV), which exist in the genome of pigs, are produced as infectious virions from all porcine cells and cause zoonosis. Here, we examined the possibility of zoonosis of hosts under conditions of immune suppression or xenotransplantation of cells producing host-adapted viruses. Upon transplantation of PERV-producing porcine cells into mice, no transmission of PERV was detected, whereas, transmission of PERV from mice transplanted with mouse-adapted PERV-producing cells was detected. In addition, the frequency of PERV transmission was increased in CsA treated mice transplanted with PERV-producing murine cells, compared with PERV-producing porcine cells. Transmission of PERV to host animals did not affect weight but immune responses, in particular, the number of T cells from PERV-transmitted mice, were notably reduced. The observed risk of PERV zoonosis highlights the requirement for thorough evaluation of viral zoonosis under particular host conditions, such as immunosuppressive treatment and transplantation with host-adapted virus-producing cells.

Highlights

  • Xenotransplantation offers the possibility to overcome the shortage of human donor organs [1]

  • The possibility of misleading results on Porcine endogenous retroviruses (PERV) detection owing to contamination of transplanted cells was discounted based on negative PCR results for neomycin or porcine mitochondrial cytochrome oxidase subunit II (COII) gene in PERV-positive organs

  • Following incubation of sera from mice transplanted with PERV/NIH3T3 cells on top of a transwell membrane, detection of PERV in 293T cells at the bottom provided evidence that the virus particles migrate through the membrane and infect cells

Read more

Summary

Introduction

Xenotransplantation offers the possibility to overcome the shortage of human donor organs [1]. Pigs are preferentially used for xenotransplantation because of ethical considerations, breeding characteristics, compatible organ sizes, and physiology [2, 3]. Several obstacles, such as immunological barriers and the possibility of viral zoonosis, need to be addressed for successful xenotransplantation [4,5,6]. Genetically modified pigs lacking a major xenoantigen have been developed [7, 8]. The risk of viral zoonosis remains and is even increased in pigs that are genetically engineered to reduce host-versus-graft reactions [9].

Methods
Results
Conclusion

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.