Porcine Endogenous Retrovirus Transmission Characteristics of an Inbred Herd of Miniature Swine

Abstract

Here we report the identification of inbred miniature swine that failed to produce human-tropic replicationcompetent porcine endogenous retroviruses (HTRC PERVs), using in vitro coculture assays. When HTRC PERVs were isolated from transmitting animals, all were recombinant viruses, with the receptor-binding domain of PERV-A combining with PERV-C-related sequences.

Identification of receptors for pig endogenous retrovirus

“…Previous reports have demonstrated that immunodeficient mice transplanted with pig islets can be infected by PERV but without evidence of productive infection (31,32). It remains to be determined whether this infection represents infection of the mouse cells with PERV-A or whether it is the result of limited replication of PERV-B or -C. Although a functional PERV-B receptor has been demonstrated on murine cells (5), the isolation of replication-competent PERV-B from transmission assays with primary pig cells such as the pig islets used in one of the studies has not been reported (6,7,30).…”

“…(i) Replication competent PERV: The replication-competent PERV-A 14͞220 was isolated in 293 cells after their infection by PERV released from peripheral blood mononuclear cells (PBMCs) of an inbred miniature swine (7). This culture contains two PERV-A species, both of which possess the env receptor binding domains of PERV-A in combination with the remaining env sequences of PERV-C (GenBank accession nos.…”

“…We sought to identify the receptor used by PERV-A, because all human-tropic PERV isolates obtained from primary pig cells have been PERV-A (6,7), and this subgroup of virus is present in porcine DNA at a higher copy number than PERV-B (4). Thus, it is likely that PERV-A represents the primary PERV subgroup for which humans are at risk in the context of pig-tissue xenotransplantation.…”

Cell Replacement Therapy: The Rationale for Encapsulated Porcine Islet Transplantation

“…The possible transmission of these retroviruses to humans, and their as yet unknown consequences in recipients, have given rise to some concerns over the safety of xenotransplantation, particularly in view of reports that PERVs from certain pig strains can infect human cells in vitro (Patience et al 1997;Martin et al 1998a) and that immune-incompetent SCID (severe combined immunodeficiency) mice may develop either microchimerism or infection in vivo (van der Laan et al 2000). The in vitro findings have, however, been shown to be strain-specific (Patience 2001;Clemenceau et al 2001;Oldmixon et al 2002) and cells from animals studied by LCT have not shown retrovirus infectivity. Moreover, no evidence of PERV transmission has been detected over 200 patients who have been exposed to pig cells or tissues and tested for evidence of PERV infection using sensitive detection methods (Wynyard et al 2011;Garkavenko et al 2008b;Denner 2003;Dinsmore et al 2000;Heneine et al 1998;Heneine et al 2001;Irgang et al 2003;Martin et al 1998b;Paradis et al 1999;Patience et al 1998;Tacke et al 2001).…”

Developing Xenostandards for Microbiological Safety: New Zealand Experience

“…Another important aspect to consider is the ability of PERV-A and PERV-C to recombine as there is evidence that PERV A/C recombinants show higher titres when cultured in human cells in vitro (Bartosch et al, 2004;Oldmixon et al, 2002;Wilson, Wong, VanBrocklin, & Federspiel, 2000;Wood et al, 2004). As discussed earlier, using the co-culture infectivity test with human HEK293 and swine St Iowa target cell lines, it was established that primary cells (PBMCs) from NZ donor pigs do not release either xeno-or ecotropic infective viruses Garkavenko, Wynyard, Nathu, Simond, et al, 2008).…”