Restriction of Porcine Endogenous Retrovirus by Porcine APOBEC3 Cytidine Deaminases

Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses

“…It was found that PERV was significantly inhibited by various porcine A3s in single-round as well as spreading virus assays. PERV inhibition strongly correlated with a specific cytidine deamination in viral genomes for the trinucleotides 5=TGC (edited nucleotide is underlined), for poA3Z2 as well as poA3Z2-Z3, and 5=CAC, for A3Z3 (93,94,179). These results strongly implicate that human and porcine A3s can inhibit PERV replication in vivo, thereby reducing the risk of potential infection of human cells by PERV in the course of pig-to-human xenotransplantation.…”

“…Furthermore, it was reported that overexpressed poA3Z2-Z3 did not significantly interfere with PERV transmission, and it was concluded that PERV was resistant to its species-specific A3 protein (150). Subsequently, the chromosomal porcine A3 locus for poA3Z2 and poA3Z3 was reanalyzed (93,94). Data showed that pigs express four different A3 mRNAs, encoding poA3Z2 and poA3Z3 and, by readthrough transcription and alternative splicing, poA3Z2-Z3 and poA3Z2-Z3 splice variant A (SVA).…”

Porcine endogenous retroviruses: What are the risks of infection transmission in xenotransplantation?

“…The intact immune system of humans must be able to eliminate PERV infection, for example, by APOBEC proteins or tetherin Dorrschuck et al, 2011). Nevertheless, it is unknown whether PERV infection is able to decrease congenital virus induced immunity in xenograft patients.…”

“…The infectious titer of PERV obtained from por cine cells is extremely low compared to the titers of other retroviruses (Blush et al, 2002). Porcine cells are able to resist PERV infection, for example, with the help of proteins of inducible cytidinic deaminases from the APOBEC family (Dorrschuck et al, 2011) or proteins of tetherin . Proteins from the APOBEC family are important for congeni tal virus induced immunity and are capable of induc ing numerous mutations of cytidine into uridine within the DNA of the provirus.…”

Methods and Tools for Detection and Evaluation of the Risks of Porcine Endogenous Retrovirus in Porcine to Human Xenotransplantation

“…Another restriction factor identified initially in studies with HIV is called APOBEC -it is packaged into viral particles and inhibits viral replication by editing cytosine residues through its deaminase activity (reviewed in (Goila-Gaur and Strebel 2008)). Recently, the porcine APOBEC proteins were identified and analyzed for their ability to restrict PERV replication and it was shown that they were packaged into the PERV virions and edited certain cytosine residues, suggesting that this may be a mechanism by which porcine cells restrict this endogenous retrovirus (Dorrschuck, Fischer et al 2011). Although some have hypothesized that human APOBEC may restrict PERV replication to account for the observed lack of transmission in human xenotransplantation clinical trial participants (see section 2.2.4), a detailed study to determine whether human APOBEC might also restrict PERV has not been performed, to date.…”