Packaging of human endogenous retrovirus sequences is undetectable in porcine endogenous retrovirus particles produced from human cells

Abstract

The chronic shortage of human donor organs and tissues for allotransplantation could be relieved if clinical xenotransplantation were to become a viable clinical therapy. Balanced against the benefits of xenotransplantation are the possible consequences of zoonotic infections, and in particular, infection by porcine endogenous retrovirus (PERV). An often-proclaimed risk of PERV infection is the possible recombination of PERV with human endogenous retroviruses (HERV). To address this issue, we examined the potential for HERV sequences to be cross-packaged into PERV particles produced from infected human 293 cells. Although HERV-K, W, E, R, and ERV-9 RNA transcripts are expressed in 293 cells, we did not detect cross-packaging of any of these HERV groups. Quantitative analysis indicated that less than approximately 1 in 10(4)-10(7) PERV particles might contain HERV sequences. In comparison, we found that murine leukemia virus (MLV)-based vector transcripts were cross-packaged at a rate of approximately one copy in 10(4) PERV particles. Our results indicate that the potential for recombination of PERV and HERV sequences is low and that novel viruses generated by this mechanism are unlikely to represent a significant risk for xenotransplantation.

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

“…On the other hand, only a truncated version of HIV env is capable of pseudotyping MuLV virions, though the potential of this occurring in a natural state is unknown (47). There is only one study suggesting that PERV virions do not efficiently package human endogenous retrovirus sequences (48). Thus, there is a possibility that PERV could be pseudotyped in human patients by complementation with human endogenous retrovirus envelope sequences encoded by human endogenous retrovirus (HERV-W) (49,50), HERV-E (51) or HERV-K (52) and expressed as functional proteins in different human tissues.…”

Evidence and controversies on the role of XMRV in prostate cancer and chronic fatigue syndrome

“…Therefore, the potential risk of human infection due to xenotransplantation cannot be ignored [110]. It is not clear whether PERV and XMRV could recombine, although copackaging and pseudotyping between PERV and murine retroviruses has been described [111,112]. Although there is about 53% sequence identity between PERV and XMRV, regions of higher homology present in both viruses would facilitate recombination.…”

Selective Inhibition of Porcine Endogenous Retrovirus Replication in Human Cells by Acyclic Nucleoside Phosphonates

“…Thus, it seems premature to exclude the possibility of PERV transmission from donor organs to recipients upon xenotransplantation. Furthermore, it is also possible that recombination between PERV and human endogenous retrovirus generates novel retroviruses pathogenic to humans (23).…”