- Email: [email protected]
Response from Sandstrom and Chapman
COMMENT
Another treatment, which is more likely to satisfy both patients and scientists, has recently been described8. Here, liver failure was restored with a so-called ‘bioartificial liver’, using porcine hepatocytes and a charcoal column, while the patient was awaiting transplantation with a suitable human liver. This device, although temporary, and not for use outside hospital settings, should reduce the chances of porcine viruses being transmitted. This cannot be said for the practice of transplanting pig neural cells into patients suffering from Parkinson’s disease9, where longterm graft survival has been achieved.
Virus transmission was not studied in these cases, and, although ‘mad pig disease’ has not yet been described, large-scale xenotransplantation of neural tissue also generates the danger of putative prion disease transmission to recipients.
Antoinette C. van der Kuyl and Jaap Goudsmit Dept of Human Retrovirology, Academic Medical Centre, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands
Response from Sandstrom and Chapman
D
r Onions and colleagues1 infer, from knowledge about feline leukemia virus (FeLV) and murine leukemia virus (MuLV) infections, what might be expected if porcine endogenous retrovirus (PoERV) infections occur in humans. While the capacity of PoERV to infect humans remains unproven2,3, the reasoning of Onions et al. argues for investigation of three hypotheses. First, PoERV infections might be expected to be largely abortive. Exploration of the feasibility and efficacy of transient clinical interventions intended to decrease the likelihood that persistent infection will be established (such as peritransplant prophylactic antiretroviral treatment) might be warranted. Second, it may be possible to prevent PoERV infection in recipients of porcine xenografts through pre-transplant vaccination. Third, the presence of FeLV in the saliva of infected cats indicates that hepatitis B or cytomegalovirus infections might provide more appropriate models than human retroviruses for infection control practices following human exposure to PoERV. Sexual or parenteral blood exposure is necessary for transmission of HIV and human Tcell lymphotropic virus (HTLV) infections, and saliva poses a negligible threat. Dr Takeuchi4 cautions that the exact behavior of a microorganism when it crosses a species barrier cannot be predicted. Nevertheless, current knowledge supports the exploration of the first two hypotheses and warrants attention to the third hypothesis
TRENDS
IN
during the development of infection control guidelines for porcine xenograft recipients. Drs van der Kuyl and Goudsmit5 highlight the development of pigs transgenically engineered to circumvent hyperacute rejection (HAR), a modification anticipated to facilitate graft survival but also to compromise lytic complement clearance of PoERV (Refs 1,6). Recipients of xenografts from nontransgenic pigs, the only population studied to date2,3, represent the lowest end of a spectrum of risk for PoERV infection. Risks will need to be independently assessed for alternative xenograft applications, including the use of transgenic pigs. Drs van der Kuyl and Goudsmit5 also discuss a study by Allan et al. of human recipients of baboon livers7. The important contribution of this work is recognition of the persistent presence of simian foamy virus (SFV) and baboon endogenous retrovirus (BaEV), constituting potentially ongoing niduses for human infection following receipt of baboon xenografts. Given that humans have been infected with SFV of baboon origin following transient occupational exposures8, it is highly likely that this more intimate ongoing exposure would result in infection. Furthermore, SFV can infect humans and is not eliminated from persistently microchimeric baboon cells. SFV infection has never been associated with disease in any species, including humans. Nevertheless, in light of this knowledge, intentional or negligent
MICROBIOLOGY
432
References 1 Brown, J. et al. (1998) Trends Microbiol. 6, 411–415 2 Zaidi, A. et al. (1998) Transplantation 65, 1584–1590 3 Allan, J.S. (1996) Nat. Med. 2, 18–21 4 Stoye, J.P. (1997) Nature 386, 126–127 5 Weiss, R.A. (1998) Nat. Med. 4, 391–392 6 Vanderpool, H.Y. (1998) Lancet 351, 1347–1350 7 Allan, J.S. et al. (1998) AIDS Res. Hum. Retrovir. 14, 821–824 8 Chen, S.C. et al. (1997) Ann. New York Acad. Sci. 831, 350–360 9 Deacon, T. et al. (1997) Nat. Med. 3, 350–353
exposure of humans to foamyvirus-infected xenografts would be hard to justify and is unlikely to be allowed by regulatory bodies. These studies also support the need for assessment of BaEV infection among humans exposed to baboons or baboon tissue. The FDA requires all porcine xenograft recipients in the USA to be monitored for PoERV infections, including the recipients of porcine neuronal tissue reported by Deacon and colleagues9. These negative results, although unpublished, have been presented in public forums.
Paul A. Sandstrom and Louisa E. Chapman HIV/Retrovirus Diseases Branch, Divn of AIDS, STD and TB Laboratory Research, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA References 1 Onions, D. et al. (1998) Trends Microbiol. 6, 431 2 Patience, C. et al. (1998) Lancet 352, 699–701 3 Heneine, W. et al. (1998) Lancet 352, 695–699 4 Takeuchi, Y. (1998) Trends Microbiol. 6, 430 5 van der Kuyl, A.C. and Goudsmit, J. (1998) Trends Microbiol. 6, 431–432 6 Patience, C., Takeuchi, Y. and Weiss, R.A. (1997) Nat. Med. 3, 282–286 7 Allan, J.S. et al. (1998) AIDS Res. Hum. Retrovir. 14, 821–824 8 Heneine, W. et al. (1998) Nat. Med. 4, 391–392 9 Deacon, T. et al. (1997) Nat. Med. 3, 350–353
VOL. 6 NO. 11 NOVEMBER 1998
Another treatment, which is more likely to satisfy both patients and scientists, has recently been described8. Here, liver failure was restored with a so-called ‘bioartificial liver’, using porcine hepatocytes and a charcoal column, while the patient was awaiting transplantation with a suitable human liver. This device, although temporary, and not for use outside hospital settings, should reduce the chances of porcine viruses being transmitted. This cannot be said for the practice of transplanting pig neural cells into patients suffering from Parkinson’s disease9, where longterm graft survival has been achieved.
Virus transmission was not studied in these cases, and, although ‘mad pig disease’ has not yet been described, large-scale xenotransplantation of neural tissue also generates the danger of putative prion disease transmission to recipients.
Antoinette C. van der Kuyl and Jaap Goudsmit Dept of Human Retrovirology, Academic Medical Centre, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands
Response from Sandstrom and Chapman
D
r Onions and colleagues1 infer, from knowledge about feline leukemia virus (FeLV) and murine leukemia virus (MuLV) infections, what might be expected if porcine endogenous retrovirus (PoERV) infections occur in humans. While the capacity of PoERV to infect humans remains unproven2,3, the reasoning of Onions et al. argues for investigation of three hypotheses. First, PoERV infections might be expected to be largely abortive. Exploration of the feasibility and efficacy of transient clinical interventions intended to decrease the likelihood that persistent infection will be established (such as peritransplant prophylactic antiretroviral treatment) might be warranted. Second, it may be possible to prevent PoERV infection in recipients of porcine xenografts through pre-transplant vaccination. Third, the presence of FeLV in the saliva of infected cats indicates that hepatitis B or cytomegalovirus infections might provide more appropriate models than human retroviruses for infection control practices following human exposure to PoERV. Sexual or parenteral blood exposure is necessary for transmission of HIV and human Tcell lymphotropic virus (HTLV) infections, and saliva poses a negligible threat. Dr Takeuchi4 cautions that the exact behavior of a microorganism when it crosses a species barrier cannot be predicted. Nevertheless, current knowledge supports the exploration of the first two hypotheses and warrants attention to the third hypothesis
TRENDS
IN
during the development of infection control guidelines for porcine xenograft recipients. Drs van der Kuyl and Goudsmit5 highlight the development of pigs transgenically engineered to circumvent hyperacute rejection (HAR), a modification anticipated to facilitate graft survival but also to compromise lytic complement clearance of PoERV (Refs 1,6). Recipients of xenografts from nontransgenic pigs, the only population studied to date2,3, represent the lowest end of a spectrum of risk for PoERV infection. Risks will need to be independently assessed for alternative xenograft applications, including the use of transgenic pigs. Drs van der Kuyl and Goudsmit5 also discuss a study by Allan et al. of human recipients of baboon livers7. The important contribution of this work is recognition of the persistent presence of simian foamy virus (SFV) and baboon endogenous retrovirus (BaEV), constituting potentially ongoing niduses for human infection following receipt of baboon xenografts. Given that humans have been infected with SFV of baboon origin following transient occupational exposures8, it is highly likely that this more intimate ongoing exposure would result in infection. Furthermore, SFV can infect humans and is not eliminated from persistently microchimeric baboon cells. SFV infection has never been associated with disease in any species, including humans. Nevertheless, in light of this knowledge, intentional or negligent
MICROBIOLOGY
432
References 1 Brown, J. et al. (1998) Trends Microbiol. 6, 411–415 2 Zaidi, A. et al. (1998) Transplantation 65, 1584–1590 3 Allan, J.S. (1996) Nat. Med. 2, 18–21 4 Stoye, J.P. (1997) Nature 386, 126–127 5 Weiss, R.A. (1998) Nat. Med. 4, 391–392 6 Vanderpool, H.Y. (1998) Lancet 351, 1347–1350 7 Allan, J.S. et al. (1998) AIDS Res. Hum. Retrovir. 14, 821–824 8 Chen, S.C. et al. (1997) Ann. New York Acad. Sci. 831, 350–360 9 Deacon, T. et al. (1997) Nat. Med. 3, 350–353
exposure of humans to foamyvirus-infected xenografts would be hard to justify and is unlikely to be allowed by regulatory bodies. These studies also support the need for assessment of BaEV infection among humans exposed to baboons or baboon tissue. The FDA requires all porcine xenograft recipients in the USA to be monitored for PoERV infections, including the recipients of porcine neuronal tissue reported by Deacon and colleagues9. These negative results, although unpublished, have been presented in public forums.
Paul A. Sandstrom and Louisa E. Chapman HIV/Retrovirus Diseases Branch, Divn of AIDS, STD and TB Laboratory Research, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA References 1 Onions, D. et al. (1998) Trends Microbiol. 6, 431 2 Patience, C. et al. (1998) Lancet 352, 699–701 3 Heneine, W. et al. (1998) Lancet 352, 695–699 4 Takeuchi, Y. (1998) Trends Microbiol. 6, 430 5 van der Kuyl, A.C. and Goudsmit, J. (1998) Trends Microbiol. 6, 431–432 6 Patience, C., Takeuchi, Y. and Weiss, R.A. (1997) Nat. Med. 3, 282–286 7 Allan, J.S. et al. (1998) AIDS Res. Hum. Retrovir. 14, 821–824 8 Heneine, W. et al. (1998) Nat. Med. 4, 391–392 9 Deacon, T. et al. (1997) Nat. Med. 3, 350–353
VOL. 6 NO. 11 NOVEMBER 1998