Response from Sandstrom and Chapman

Abstract

Dr Onions and colleagues[1xOnions, D. et al. Trends Microbiol. 1998; 6: 431Abstract | Full Text | Full Text PDF | PubMedSee all References[1]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 unproven[2xPatience, C. et al. Lancet. 1998; 352: 699–701Abstract | Full Text | Full Text PDF | PubMedSee all References, 3xHeneine, W. et al. Lancet. 1998; 352: 695–699Abstract | Full Text | Full Text PDF | PubMedSee all References], 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 T-cell lymphotropic virus (HTLV) infections, and saliva poses a negligible threat. Dr Takeuchi[4xTakeuchi, Y. Trends Microbiol. 1998; 6: 430Abstract | Full Text | Full Text PDF | PubMedSee all References[4]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 during the development of infection control guidelines for porcine xenograft recipients.Drs van der Kuyl and Goudsmit[5xvan der Kuyl, A.C. and Goudsmit, J. Trends Microbiol. 1998; 6: 431–432Abstract | Full Text | Full Text PDF | PubMed | Scopus (3)See all References[5]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 [1xOnions, D. et al. Trends Microbiol. 1998; 6: 431Abstract | Full Text | Full Text PDF | PubMedSee all References, 6xPatience, C., Takeuchi, Y., and Weiss, R.A. Nat. Med. 1997; 3: 282–286Crossref | PubMed | Scopus (819)See all References]). Recipients of xenografts from nontransgenic pigs, the only population studied to date[2xPatience, C. et al. Lancet. 1998; 352: 699–701Abstract | Full Text | Full Text PDF | PubMedSee all References, 3xHeneine, W. et al. Lancet. 1998; 352: 695–699Abstract | Full Text | Full Text PDF | PubMedSee all References], 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 Goudsmit[5xvan der Kuyl, A.C. and Goudsmit, J. Trends Microbiol. 1998; 6: 431–432Abstract | Full Text | Full Text PDF | PubMed | Scopus (3)See all References[5]also discuss a study by Allan et al. of human recipients of baboon livers[7xAllan, J.S. et al. AIDS Res. Hum. Retrovir. 1998; 14: 821–824Crossref | PubMedSee all References[7]. 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 exposures[8xHeneine, W. et al. Nat. Med. 1998; 4: 391–392Crossref | PubMed | Scopus (157)See all References[8], 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 exposure of humans to foamy-virus-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 colleagues[9xDeacon, T. et al. Nat. Med. 1997; 3: 350–353Crossref | PubMed | Scopus (347)See all References[9]. These negative results, although unpublished, have been presented in public forums.