Review
Virology
Joachim Denner
Summary: PERVs, present in all pigs, raise risks for xenotransplantation, but no transmission has been observed in clinical or preclinical trials. Strategies like selecting PERV-C-free animals and using antiviral drugs have been developed, but further experimental evaluation is needed before moving to the clinic.
Article
Immunology
Hao Feng, Tao Li, Jiaxiang Du, Qiangbing Xia, Lu Wang, Song Chen, Lan Zhu, Dengke Pan, Yi Wang, Gang Chen
Summary: This study reveals the significance of Sda in pig-to-rhesus monkey xenotransplantation, highlighting the role of natural and induced anti-Sda antibodies in the immune response during transplantation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Virology
Luise Krueger, Johanna Boettger, Christene A. Huang, Joachim Denner
Summary: PERVs-A and -B are integrated in all pigs' genome, while PERV-C is found in many but not all pigs. Some pig cell lines have been shown to release virus particles that are able to infect human cells, with some being recombinant PERV-A/C. Analysis of three pig lymphoma cell lines showed that they all contained PERV-A, PERV-B, and PERV-C proviruses, with only one cell line harboring PERV-A/C recombinants. Expression at the RNA level was minimal, and no protein expression or virus particle release was observed, indicating that PERVs may not be involved in the pathogenesis of these lymphomas.
Article
Virology
Sabrina Halecker, Ludwig Krabben, Yannick Kristiansen, Luise Krueger, Lars Moller, Dietmar Becher, Michael Laue, Benedikt Kaufer, Christian Reimer, Joachim Denner
Summary: The study shows that the human-tropic recombinant PERV-A/C proviruses can only be found in a very small number of minipigs, but not in other pigs, and the isolation of these viruses as infectious agents that can replicate in human cells is an extremely rare event.
Article
Multidisciplinary Sciences
Luhan Yang, George Church, Hong-Ye Zhao, Lusheng Huang, Yangbin Gao, Hong-Jiang Wei, Geoffrey Yang
Summary: Germline editing, the process of editing an individual's genome to create heritable changes, has been extensively applied to modify the pig genome, serving as a model system to study methodologies, applications, and challenges of mammalian germline genome editing. The broad implications of animal germline editing and its potential clinical applications are also discussed in this context.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Microbiology
Sabrina Halecker, Julia Metzger, Christina Strube, Ludwig Krabben, Benedikt Kaufer, Joachim Denner
Summary: Minipigs play a crucial role in biomedical research and xenotransplantation, with Mini-LEWE minipigs showing fewer viruses and lacking PERV-A/C compared to other breeds.
Article
Biochemistry & Molecular Biology
Hien Lau, Shiri Li, Nicole Corrales, Samuel Rodriguez, Mohammadreza Mohammadi, Michael Alexander, Paul de Vos, Jonathan Lakey
Summary: Nec-1 supplementation has positive effects on both the in vitro and in vivo function of isolated PPIs, especially when added on day 3 of culture. It significantly improves islet recovery, proliferation and differentiation of endocrine cells. The use of Nec-1 can shorten time to normoglycemia, improve glycemic control, and increase circulating insulin levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Genetics & Heredity
Yu Liu, Yifan Niu, Xiang Ma, Yun Xiang, De Wu, Weifen Li, Tao Wang, Dong Niu
Summary: Xenotransplantation using porcine organs is a promising solution to the organ shortage for human transplantation. However, the presence of porcine endogenous retrovirus (PERV) poses a major microbiological risk. This review summarizes the current progress on PERVs, including their classification, molecular structure, regulation, immune system function, and potential risks in xenotransplantation. The insufficient study on PERVs and the unanswered questions for future research are also discussed.
FUNCTIONAL & INTEGRATIVE GENOMICS
(2023)
Article
Virology
Hina Jhelum, Martin Bender, Bruno Reichart, Maren Mokelke, Julia Radan, Elisabeth Neumann, Ludwig Krabben, Jan-Michael Abicht, Benedikt Kaufer, Matthias Laengin, Joachim Denner
Summary: Xenotransplantation involves the presence of donor cells in the recipient's body, and distinguishing between microchimerism and PERV infection is challenging. This study presents virological methods for identifying microchimerism and excluding PERV infection in baboons after pig heart transplantation. Screening for porcine cellular genes and detecting infection using porcine SINEs proved effective, and the absence of PERV RNA and antibodies further confirmed the absence of infection.
Review
Virology
Joachim Denner
Summary: Porcine endogenous retroviruses (PERVs) cannot be eliminated by traditional methods and originated from transspecies transmission of precursor retroviruses from different animals, further evolving in the pig genome. The transmissibility and pathogenesis of PERVs are closely linked to their long terminal repeats (LTRs) and envelope recombination.
ARCHIVES OF VIROLOGY
(2021)
Article
Medicine, General & Internal
Kenji Matsui, Yoshitaka Kinoshita, Yuka Inage, Naoto Matsumoto, Keita Morimoto, Yatsumu Saito, Tsuyoshi Takamura, Hitomi Matsunari, Shuichiro Yamanaka, Hiroshi Nagashima, Eiji Kobayashi, Takashi Yokoo
Summary: Fetal porcine kidneys injected with human nephron progenitor cells could be a viable option for kidney transplantation; using a model of freezing and transplantation, we demonstrated that the differentiation potency of vitrified fetal porcine kidneys could be evaluated, providing a practical protocol to assess the quality of individual lots.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Virology
Joachim Denner, Hendrik Jan Schuurman
Summary: Minipigs play a crucial role in biomedical research and xenotransplantation, but virus safety is a concern. While most porcine viruses can be eliminated, porcine endogenous retroviruses (PERVs) remain a challenge. It is recommended to use PERV-C negative pig donors in clinical xenotransplantation to avoid potential risks.
Article
Biotechnology & Applied Microbiology
Wenhao Wang, Jiansen Lu, Ying Song, Chun Zeng, Yongkui Wang, Cheng Yang, Bin Huang, Yifan Dai, Jian Yang, Liangxue Lai, Liping Wang, Daozhang Cai, Xiaochun Bai
Summary: In this study, GTKO pig cancellous bone showed advantages in repairing femoral condyle bone defects and inhibiting xenotransplant rejection. Compared with WT pig bone, GTKO pig bone had reduced heterologous immunogenicity, tightly integrated with the defect, and showed better osseointegration with an appropriate rate of resorption. Additionally, GTKO pig bone promoted new bone formation.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Virology
Sabina Galka, Ewa Nowak, Ilona Bednarek
Summary: This study analyzed the relationship between the provirus genes sequences from pig cell lines and the embedded sequence of this retrovirus in infected human cells. The study found that the degree of PERV infection is related to the conservation of gene sequences, which is important for ensuring safe xenotransplantation.
Article
Cell Biology
Shuwen Zheng, Haiwen Zhong, Xiaoqing Zhou, Min Chen, Wansheng Li, Yin Zi, Yue Chi, Jinling Wang, Wei Zheng, Qingjian Zou, Liangxue Lai, Chengcheng Tang
Summary: This study used cytosine base editor (CBE) to edit the porcine endogenous retrovirus (PERV) genome in pigs, reducing cytotoxic effects. The results showed that using CBE can significantly improve the efficiency of PERV knockout and avoid severe DNA damage in pig cells.