Xenotransplantation von Zellen, Geweben oder Organen

Journal of General Virology

Brem³

et al. 2003

Prevention of cross-species infection of porcine endogenous retroviruses (PERV) is crucial for xenotransplantation. The potential risk of infection is caused by replication-competent PERV as well as by hybrid viruses derived from recombination events of distinct PERV genomes. Recently, human-tropic, replication-competent PERV genomes obtaining hybrid sequences have been observed. Here, complete polymorphism pattern analysis was performed on the full-length PERV c1 clones and on the complete envelope (env) gene sequences published to date. Several recombined full-length clones and a high number of different recombination patterns in the env gene were identified. In addition, recombinations with retroviral genomes not yet known were found. Thus, the potential risk of infection also exists for recombination products, including defective PERV loci.

Section: Introductionmentioning

confidence: 99%

Recombination analysis of human-tropic porcine endogenous retroviruses

Klymiuk

Journal of General Virology

Brem³

et al. 2003

“…In pigs, retroviral recombination is thought to be involved in generating novel retroviral genomes with unknown consequences for host tropism and pathology (18,20,25). The use of genetically modified animals in xenotransplantation has been suggested to enhance the potential risk of ERV transmission (3). In addition, ERV contamination has been found in biomedical products derived from different species, including pigs (12,32) and chicken (15), but no infectious particles have been detected.…”

mentioning

confidence: 99%

Characterization of Endogenous Retroviruses in Sheep

Klymiuk

Brem³

et al. 2003

J Virol

Endogenous retrovirus (ERV) sequences have been found in all mammals. In vitro and in vivo experiments revealed ERV activation and cross-species infection in several species. Sheep (Ovis aries) are used for various biotechnological purposes; however, they have not yet been comprehensively screened for ERV sequences. Therefore, the aim of the study was to classify the ERV sequences in the ovine genome (OERV) by analyzing the retroviral pro-pol sequences. Three OERV ␤ families and nine OERV ␥ families were revealed. Novel open reading frames (ORF) in the amplified proviral fragment were found in one OERV ␤ family and two OERV ␥ families. Hybrid OERV produced by putative recombination events were not detected. Quantitative analysis of the OERV sequences in the ovine genome revealed no relevant variations in the endogenous retroviral loads of different breeds. Expression analysis of different tissues from fetal and pregnant sheep detected mRNA from both gammaretrovirus families, showing ORF fragments. Thus, the release of retroviruses from sheep cells cannot be excluded.

“…Prerequisites are the solution of the severe host-versus-graft reactions and the prevention of the cross-species transfer of pathogens via the transplant. Use of specific-pathogen-free animals focuses the potential risk of infection to the porcine endogenous retroviral sequences (PERV) (2).…”

mentioning

confidence: 99%

Characterization of Porcine Endogenous Retrovirus γ pro-pol Nucleotide Sequences

Klymiuk¹,

Brem³

et al. 2002

J Virol

Endogenous retroviral sequences in the pig genome (PERV) represent a potential infectious risk in xenotransplantation. All known infectious PERV have been asssigned to the PERV ␥1 family, consisting of the subfamilies A, B, and C. The aim of the study was the concise examination of PERV ␥ by the analysis of the retroviral pro-pol sequences. The analysis of 52 pro-pol clones amplified in this study revealed eight PERV ␥ families. In addition to four already-described families (␥1, ␥4, ␥5, ␥6), four novel families (␥7, ␥8, ␥9, ␥10) were identified. Quantitative analysis of the novel PERV ␥ sequences in selected breeds revealed variations in the endogenous retroviral load. Open reading frames (ORF) in the amplified proviral fragment were only found for PERV ␥1. In addition, novel ORF-containing PERV ␥1 clones consisting of hybrid sequences were revealed. Sequence comparison from published full-length PERV ␥1 clones of the PERV subfamilies A, B, and C resulted in a lack of strict correlation of the classification of pro-pol and env. The results indicated the occurrence of causative recombination events between retroviral genomes. Thus, our study on PERV ␥ provides new data for the evaluation and selection of pigs intended to be used in xenotransplantation.