Retrotransposition: another obstacle for xenotransplantation?
To overcome the shortage of human organs for transplantation, pigs are considered as xenogeneic donors. However, primarily immunological and virological barriers exist. One of the main virological obstacles, represented by the presence of functional and infectious porcine endogenous retroviruses (PERV) in the genome of the pigs, may be excluded by conventional breeding. In contrast, there are truncated proviral sequences that have the capacity to retrotranspose, causing insertional mutagenesis in the xenograft and in infected human cells. To estimate this risk we have investigated the potential of PERV to retrotranspose. Moloney Murine Leukemia Virus (MoMLV), a gamma type retrovirus and close relative to PERV, which has been described as able to retrotranspose, was implemented as a control. First results based on a neomycin indicator monitoring system indicate that PERV is able to retrotranspose at higher frequencies compared with MoMLV.
Jungmann
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Paul-Ehrlich-Institut, Langen, Germany.
Tönjes
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D017398:Alternative Splicing; D000818:Animals; D020077:Endogenous Retroviruses / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D007438:Introns; D012190:Retroviridae / Q000235:genetics* / Q000472:pathogenicity; D012192:Retroviridae Infections / Q000517:prevention & control / Q000635:transmission*; D013552:Swine; D014183:Transplantation, Heterologous / Q000009:adverse effects* / Q000592:standards