A mouse virus, XMRV, closely related to porcine endogenous retroviruses in the human population – A new risk for xenotransplanation? – Source: Xenotransplanation, Feb 22, 2011

[Note: Xenotransplantation is the transplantation of living cells, tissues or organs from one species to another – most frequently in current medical practice, from pigs to humans. A transplant of human to human would be an allotransplant.]

There is a need to carefully consider the potential infectious risks associated with xenotransplantation.

Whereas known viruses can easily be eliminated from donor pigs by designated pathogen free breeding of the animals, this is not possible for porcine endogenous retroviruses (PERVs) integrated into the genome of all pigs and unknown viruses.

PERVs infect human cells in vitro [in laboratory cultures] and may theoretically – like many retroviruses – induce immunodeficiencies and/or tumors.

Recently a xenotropic murine leukemia virus related virus (XMRV), a gammaretrovirus that is closely related to murine leukemia viruses as well as to PERV, has been detected in human patients with prostate carcinoma, chronic fatigue syndrome (CFS) and also in a small percentage of clinically healthy individuals.

Whereas several studies showed a broad distribution of XMRV in the USA, similar studies in Europe failed to detect this virus in the human population (for review see 1). [Note: This does not appear to consider positive European studies.] These results clearly indicate that XMRV is not causally associated with prostate carcinoma and CFS.

Either the virus is common in the USA (may be there are specific populations of rodents releasing this virus) and not in Europe, or it is a laboratory contamination.

If XMRV is indeed circulating in the human population, it has important implications for xenotransplantation.

A test should be developed to discriminate between PERV and XMRV and the potential for recombination between the two viruses should be investigated.

Recombination between the human tropic PERV-A and the ecotropic PERV-C has been described and recombinant PERV-A/C was characterized by increased replication titers.

Whether XMRV and PERV recombine remains unclear, however co-packaging and pseudotyping between PERV and murine retroviruses have been described.

This raises new questions:

• Should the xenotransplant recipient be pre-screened for XMRV to avoid recombination?

• What measures can be taken when XMRV infection is detected in such a screen?

However, before dealing with these specific details, it is necessary to address the important broad questions concerning the distribution of XMRV and its impact on human health.

1. Reference: Denner J. Detection of a gammaretrovirus, XMRV, in the human population: Open questions and implications for xenotransplantation. Retrovirology 2010; 7: 16.

Source: Xenotransplanation, Feb 22, 2011;18(1). From Berlin Symposium on Xenotransplantation. Denner J, Robert Koch Institute, Berlin, Germany.

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