Productive infection of primary human endothelial cells by pig endogenous retrovirus (PERV)

Abstract

The potential risk of viral transmission in the setting of xenotransplantation has gained major attention. Different porcine cell types have been shown to release retroviral particles, which are infectious for human cell lines in vitro. However, there are only a few data on whether PERV (pig endogenous retrovirus) is able to infect primary human cells. In this study we have analyzed endothelial cells, vascular fibroblasts, mesangial cells, mononuclear cells, hematopoetic stem cells and bone marrow stromal cells for PERV transmission. We now provide evidence for primary human endothelial cells, vascular fibroblasts, and mesangial cells to be susceptible to PERV transmission. PERV infection was productive in endothelial cells and mesangial cells. Our data confirm and extend former reports concerning the PERV infection of human cells. The PERV infection of different primary human cells represents further significant evidence for a viral risk during xenotransplantation. In this context, special attention should be directed towards productive infection of human endothelial cells: in the setting of xenotransplantation this cell type will have close contact with porcine cells and PERV particles.

Analysis of potential porcine endogenous retrovirus (PERV) transmission in a whole-organ xenotransplantation model without interfering microchimerism

“…However, first preliminary results of in vitro infection experiments using a very limited number of cell lines of 5 different primate species suggested nonhuman primate cells not to be permissive to PERV infection. Contrarily, recent data on a much broader experimental basis supplied evidence that apes, baboons, rhesus, and maybe cynomolgus monkeys are susceptible to PERV infection [15,17]. In the light of these new findings, appropriate in vivo models simulating whole-organ xenotransplantation in nonhuman primates should be applied for analysis of potential PERV in vivo infection.…”

AN69 Hollow Fiber Membrane will Reduce but Not Abolish the Risk of Transmission of Porcine Endogenous Retroviruses

“…Such infectrients and insulin, but protects the encapsulated cells tion has also been described in mink and feline cell lines, from the immune response. We investigated whether it and some primary baboon and human cells (18,31). Some would prevent the transmission of PERVs from the enstudies point to the transmission of PERVs from porcine capsulated PK15 cells to HEK293 human cells in vitro tissue to human cell lines in vitro and to immunodefiand to CD1 mice in vivo.…”

“…To avoid immune rejection, two approaches are posin the cells of other species, including humans (16,18,23). Other studies present evidence of the in vivo transsible: (i) induction of immunological tolerance, and (ii) the sequestering of islets in a capsule that excludes the mission of porcine endogenous retroviruses in immunodeficient mice (3,10,38).…”

Les xénogreffes finiront-elles par être acceptées ?

“…Cependant, un risque majeur concerne les virus endogènes intégrés dans le génome porcin: les PERV (porcin endogenous retrovirus) A, B et C. In vitro, les PERV peuvent infecter de façon productive des cellules humaines [42]. Cependant, plusieurs études menées chez des patients ayant briève-ment été en contact avec des tissus porcins n'ont pas montré de signes d'infection [43][44][45], ce qui suggère que cette transmission ne se produit pas in vivo.…”