Possible risks posed by single‐stranded DNA viruses of pigs associated with xenotransplantation

Abstract

Routine large‐scale xenotransplantation from pigs to humans is getting closer to clinical reality owing to several state‐of‐the‐art technologies, especially the ability to rapidly engineer genetically defined pigs. However, using pig organs in humans poses risks including unwanted cross‐species transfer of viruses and adaption of these pig viruses to the human organ recipient. Recent developments in the field of virology, including the advent of metagenomic techniques to characterize entire viromes, have led to the identification of a plethora of viruses in many niches. Single‐stranded DNA (ssDNA) viruses are the largest group prevalent in virome studies in mammals. Specifically, the ssDNA viral genomes are characterized by a high rate of nucleotide substitution, which confers a proclivity to adapt to new hosts and cross‐species barriers. Pig‐associated ssDNA viruses include torque teno sus viruses (TTSuV) in the Anelloviridae family, porcine parvoviruses (PPV), and porcine bocaviruses (PBoV) both in the family of Parvoviridae, and porcine circoviruses (PCV) in the Circoviridae family, some of which have been confirmed to be pathogenic to pigs. The risks of these viruses for the human recipient during xenotransplantation procedures are relatively unknown. Based on the scant knowledge available on the prevalence, predilection, and pathogenicity of pig‐associated ssDNA viruses, careful screening and monitoring are required. In the case of positive identification, risk assessments and strategies to eliminate these viruses in xenotransplantation pig stock may be needed.

The intestinal virome in children with cystic fibrosis differs from healthy controls

“…Protoparvovirus negatively correlated with weight z-scores and the only identified species of this genus was PPV. Porcine parvovirus is currently not thought to infect humans [46] and the negative correlation of Protoparvovirus with weight is more than likely reflective of an increase in PERT dosing to improve weight gain in our CF clinic. The presence of the ssDNA viruses PPV and PCV2 only in CF subjects may have unintentionally provided quality assurance of our workflow, given that they are both known to be in porcine-derived PERT products prescribed to patients with CF [31,32].…”

Sensitive detection systems for infectious agents in xenotransplantation*

“…13,65 In analogy to the antibody testing against PCMV, the recombinant glycoprotein gB1 of PLHV was produced and used as antigen and a goat serum against this protein was used for validation of the methods. 65 for pigs, they should be eliminated from the donor pigs (for review, see 25,66 ). For all these viruses, efficient PCR and real-time PCR methods with specific primers and probes were described.…”

Use of a Novel Enhanced DNA Vaccine Vector for Preclinical Virus Vaccine Investigation

“…Circoviruses have never been implicated in any human disease: although PCV-1 and PCV-2 were famously discovered in live rotavirus vaccines given to millions of children [40], and PCV-1 was shown to be able to infect a human hepatocellular carcinoma cell line [41], there was no evidence that PCV-1 infected the infants given the contaminated rotavirus vaccine [42]. There have been concerns, however, over ssDNA viruses of pigs associated with xenotransplantation in humans [43], and swine-human contacts are frequent and worldwide in agriculture. Thus, use of a circovirus such as BFDV as the source of elements for a replicating DNA expression vector, when the virus is hostrestricted to one type of birds and has never been associated with human disease, is probably more likely to be regarded as safe.…”