Xenotransplantation: is the risk of viral infection as great as we thought?

Two major hurdles remain before xenotransplantation can enter the clinic. The first is the more technical issue of being able to overcome the human immune response that leads to rejection of transplanted organs/cells from other species. The second, reviewed here, concerns the potential risk of inadvertent transfer of animal viruses present in the xenotransplant that are able to infect the human recipient. The threat from viruses is a particularly contentious topic because it poses a risk not only to those individuals who receive xenotransplants, but also to healthy individuals who come into contact, either directly or indirectly, with the xenotransplant recipient. In this review, we describe some of the virus types, in addition to the much discussed porcine endogenous retroviruses that might cross the species barrier, and assess the risk of such viruses causing disease in human hosts.

[1]  W. Heneine,et al.  Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue. The XEN 111 Study Group. , 1999, Science.

[2]  D. Klein,et al.  Proviral load determination of different feline immunodeficiency virus isolates using real‐time polymerase chain reaction: Influence of mismatches on quantification , 1999, Electrophoresis.

[3]  D. Onions,et al.  Evaluation of porcine cytomegalovirus as a potential zoonotic agent in xenotransplantation. , 1999, Transplantation proceedings.

[4]  T. Starzl,et al.  Chimerism after liver transplantation for type IV glycogen storage disease and type 1 Gaucher's disease. , 1993, The New England journal of medicine.

[5]  H. Jaffe,et al.  Risk of human immunodeficiency virus transmission from heterosexual adults with transfusion-associated infections. , 1988, JAMA.

[6]  James Cook,et al.  Interclass Transmission and Phyletic Host Tracking in Murine Leukemia Virus-Related Retroviruses , 1999, Journal of Virology.

[7]  H. Field,et al.  Newly discovered viruses of flying foxes. , 1999, Veterinary microbiology.

[8]  M. Joo,et al.  Animal models for immune defects caused by hepatitis C virus. , 2000, Molecular medicine today.

[9]  W. Maury Regulation of equine infectious anemia virus expression. , 1998, Journal of biomedical science.

[10]  D. Gerlier,et al.  Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus , 1993, Journal of virology.

[11]  C. Sherr,et al.  Isolation from the asian mouse Mus caroli of an endogenous type C virus related to infectious primate type C viruses. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[12]  R. Loertscher,et al.  A solitary plasmacytoma of donor origin arising 14 years after kidney allotransplantation , 1995, British journal of haematology.

[13]  J. Almond,et al.  Role for β2-Microglobulin in Echovirus Infection of Rhabdomyosarcoma Cells , 1998, Journal of Virology.

[14]  T. Mettenleiter Molecular biology of pseudorabies (Aujeszky's disease) virus. , 1991, Comparative immunology, microbiology and infectious diseases.

[15]  J. Mills,et al.  New World hantaviruses. , 1998, British medical bulletin.

[16]  H H Kazazian,et al.  HUGO—a midlife crisis? , 1998, Nature Genetics.

[17]  Ali S Khan,et al.  Hantavirus transmission in the United States. , 1997, Emerging infectious diseases.

[18]  H. Temin,et al.  Rate and mechanism of nonhomologous recombination during a single cycle of retroviral replication. , 1993, Science.

[19]  R. Löwer,et al.  The pathogenic potential of endogenous retroviruses: facts and fantasies. , 1999, Trends in microbiology.

[20]  S. Ikehara,et al.  A strategy for organ allografts without using immunosuppressants or irradiation. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[21]  B. Ehlers,et al.  Detection of two novel porcine herpesviruses with high similarity to gammaherpesviruses. , 1999, The Journal of general virology.

[22]  Brian Salmons,et al.  Protection of MLV vector particles from human complement. , 1999, Biochemical and biophysical research communications.

[23]  C. Porter,et al.  Sensitization of cells and retroviruses to human serum by (αl-3) galactosyltransferase , 1996, Nature.

[24]  J. McCormack,et al.  Infection of humans and horses by a newly described morbillivirus , 1995, The Medical journal of Australia.

[25]  T. Werner,et al.  Endogenous retroviral elements in human DNA. , 1990, Cancer research.

[26]  C. Parrish Host range relationships and the evolution of canine parvovirus. , 1999, Veterinary microbiology.

[27]  P. Fultz,et al.  Genetic differences accounting for evolution and pathogenicity of simian immunodeficiency virus from a sooty mangabey monkey after cross-species transmission to a pig-tailed macaque , 1992, Journal of virology.

[28]  F. Gao,et al.  Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes , 1999, Nature.

[29]  F. Cosset,et al.  Packaging of Endogenous Retroviral Sequences in Retroviral Vectors Produced by Murine and Human Packaging Cells , 1998, Journal of Virology.

[30]  E. Peterhans,et al.  Maedi-visna virus infection in sheep: a review. , 1998, Veterinary research.

[31]  Christopher D. Richardson,et al.  The human CD46 molecule is a receptor for measles virus (Edmonston strain) , 1993, Cell.

[32]  D. Klein,et al.  Accurate estimation of transduction efficiency necessitates a multiplex real-time PCR , 2000, Gene Therapy.

[33]  K. Nolte,et al.  Evidence against person-to-person transmission of hantavirus to health care workers. , 1996, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[34]  U. Liebert Measles virus infections of the central nervous system. , 1997, Intervirology.

[35]  K. Cornetta,et al.  No retroviremia or pathology in long-term follow-up of monkeys exposed to a murine amphotropic retrovirus. , 1991, Human gene therapy.

[36]  K. Cornetta,et al.  Amphotropic murine leukemia retrovirus is not an acute pathogen for primates. , 1990, Human gene therapy.

[37]  Alan S. Perelson,et al.  Rapid Clearance of Simian Immunodeficiency Virus Particles from Plasma of Rhesus Macaques , 1999, Journal of Virology.

[38]  R. Weiss,et al.  Host Range and Interference Studies of Three Classes of Pig Endogenous Retrovirus , 1998, Journal of Virology.

[39]  Peter D. Keightley,et al.  High genomic deleterious mutation rates in hominids , 1999, Nature.

[40]  Adeeba Kamarulzaman,et al.  Fatal encephalitis due to Nipah virus among pig-farmers in Malaysia , 1999, The Lancet.

[41]  J. Mason,et al.  Protection of retroviral vector particles in human blood through complement inhibition. , 1995, Human gene therapy.

[42]  R. Weiss,et al.  Endogenous Retroviruses: A Potential Problem for Xenotransplantation? a , 1998, Annals of the New York Academy of Sciences.

[43]  M. VanBrocklin,et al.  Extended Analysis of the In Vitro Tropism of Porcine Endogenous Retrovirus , 2000, Journal of Virology.

[44]  R. Wrangham,et al.  From Pan to pandemic , 1999, Nature.

[45]  J. Bergelson,et al.  Coxsackievirus B3 adapted to growth in RD cells binds to decay-accelerating factor (CD55) , 1995, Journal of virology.

[46]  V. Pathak,et al.  “Might as Well Jump!” Template Switching by Retroviral Reverse Transcriptase, Defective Genome Formation, and Recombination☆ , 1997 .

[47]  S. Brunak,et al.  env Sequences of Simian Immunodeficiency Viruses from Chimpanzees in Cameroon Are Strongly Related to Those of Human Immunodeficiency Virus Group N from the Same Geographic Area , 2000, Journal of Virology.

[48]  M. Raffeld,et al.  Helper virus induced T cell lymphoma in nonhuman primates after retroviral mediated gene transfer , 1992, The Journal of experimental medicine.