Tetherins of various species inhibit the release of porcine endogenous retrovirus from human cells.

Abstract

Pigs are considered as suitable xenotransplantation organ donors. However, the risk of pathogen transmission from pigs to human is a major concern in the transplantation of porcine tissues since it had been shown that porcine endogenous retroviruses (PERVs) can infect human cells. Tetherin has recently been described as a host restriction factor that blocks the release of virus particles from cells infected with some enveloped viruses. We compared tetherins derived from various species in their activity against PERVs by using a pseudotype assay. The results showed that (i) mammalian tetherins inhibit spread of PERVs, (ii) murine and rhesus tetherins are weaker inhibitors than canine and feline ones, (iii) human tetherin is induced by interferon alpha (IFN-α) and (iv) IFN-α treatment of 293T-PERV-PK-CIRCE cells reduced PERV release. We conclude that transgenic overexpression of tetherin combined with its induction by IFN-α may reduce the risk of PERV dissemination in xenotransplantation.