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)
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
Microbiology
Trevor T. Dean, Vitor Hugo B. Serrao, Jeffrey E. Lee
Summary: Retroviral elements from endogenous retroviruses play roles in mammalian physiology. Porcine endogenous retroviruses (PERVs) infect cultured human cells and their envelope glycoprotein structure is well conserved, indicating a potential role in placental development.
Article
Microbiology
Trevor T. Dean, Vitor Hugo B. Serrao, Jeffrey E. Lee
Summary: Structural analysis of the fusion protein of porcine endogenous retrovirus (PERV) provides insights into the fusion mechanism of the virus. The study determined the structure of the fusion domain of PERV, revealing its conservation with class I viral fusion proteins. Further analysis shows that class I viral fusion proteins cluster based on their mechanism of membrane fusion.
Article
Biochemical Research Methods
Ken Kono, Kiyoko Kataoka, Yuzhe Yuan, Keisuke Yusa, Kazuhisa Uchida, Yoji Sato
Summary: Xenogenic cell-based therapeutic products are expected to alleviate the chronic shortage of human donor organs, but concerns arise regarding the potential transmission of PERV when using living pig cells as raw materials. Not all PERV sequences in the porcine genome have the ability to infect human cells, thus high-throughput sequencing technologies are needed for evaluating the infectivity.
Review
Pharmacology & Pharmacy
Dong Niu, Xiang Ma, Taoyan Yuan, Yifan Niu, Yibin Xu, Zhongxin Sun, Yuan Ping, Weifen Li, Jufang Zhang, Tao Wang, George M. Church
Summary: Xenotransplantation of pig organs offers a potential solution to the shortage of donor organs for human patients but faces challenges such as immune rejection and the risk of porcine endogenous retrovirus transmission. Advances in genome engineering and immunosuppressive medications have the potential to overcome these barriers, leading to promising preclinical results and upcoming clinical trials for organs like islet, kidney, and heart transplantation.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Article
Virology
Luise Krueger, Monika Nowak-Imialek, Yannick Kristiansen, Doris Herrmann, Bjoern Petersen, Joachim Denner
Summary: EPSCs derived from porcine preimplantation embryos exhibit higher cellular potency and lower PERV expression levels compared to other pluripotent stem cells, irrespective of pig age.
Article
Virology
Michael Rodrigues Costa, Nicole Fischer, Antonia Gronewold, Barbara Gulich, Antonia W. Godehardt, Ralf R. Toenjes
Summary: A full-length replication-competent PERV-C provirus was characterized in Yucatan SLA(D/D) miniature swine. The provirus was chromosomally mapped, revealing differences from previously described PERV-C(1312) provirus. In vitro, the virus showed increased infectivity compared to other functional PERV-C isolates. This study provides insight for targeted gene knockout to generate PERV-C-free founder animals.
JOURNAL OF VIROLOGY
(2023)
Article
Medicine, General & Internal
Bartley P. Griffith, Corbin E. Goerlich, Avneesh K. Singh, Martine Rothblatt, Christine L. Lau, Aakash Shah, Marc Lorber, Alison Grazioli, Kapil K. Saharia, Susie N. Hong, Susan M. Joseph, David Ayares, Muhammad M. Mohiuddin
Summary: A porcine-to-human heart transplantation was performed on a 57-year-old man with nonischemic cardiomyopathy who was not eligible for standard therapeutics, including traditional allograft. The patient was successfully weaned from ECMO and the xenograft functioned normally until sudden failure on day 49 post-transplantation. Further studies are needed to identify the mechanisms responsible for the changes observed in the xenograft.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Medicine, Research & Experimental
Nicole Fischer, Barbara Gulich, Ralf R. Tonjes, Antonia W. Godehardt
Summary: The study observed a gradual decrease in viral RNA over time, while reverse transcriptase activity showed a significant reduction from day 7 onwards. The presence of wood litter enhanced the destabilization of the virus, and fresh harvested virus was found to be more stable than frozen virus stocks. Despite these findings, no infectivity was shown in the supernatant collected on day 7, suggesting that PERV-C is less stable and infectivity is reduced with decreasing reverse transcriptase activity.
XENOTRANSPLANTATION
(2022)
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
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
Biochemistry & Molecular Biology
Shabnam Ansari, Nidhi Gupta, Rohit Verma, Oinam N. Singh, Jyoti Gupta, Amit Kumar, Mukesh Kumar Yadav, Akshay Binayke, Mahima Tiwari, Neha Periwal, Vikas Sood, Shailendra Mani, Amit Awasthi, Shalimar, Baibaswata Nayak, C. T. Ranjith-Kumar, Milan Surjit
Summary: Coronavirus-induced disease-19 (COVID-19), caused by SARS-CoV-2, is a global health challenge. Human endogenous retroviruses (HERVs) play important roles in embryonic development and disease manifestation. This study found increased activity of several HERVs in SARS-CoV-2-infected cells, while the HERV-R envelope was downregulated in cell-based models and COVID-19 patients. Overexpression of HERV-R inhibits SARS-CoV-2 replication and the extracellular signal-regulated kinase (ERK) is involved in regulating its antiviral activity. The crosstalk between ERK and p38 MAPK controls the synthesis of HERV-R envelope protein, which modulates SARS-CoV-2 replication.
Review
Microbiology
Joshua A. Hayward, Gilda Tachedjian
Summary: Bats are known reservoirs of deadly human viruses, but the potential threat of bat retroviruses to humans remains unclear and requires further research. Recent reports of retroviruses circulating in bat populations are based on decades of research, and the global impact of the COVID-19 pandemic highlights the importance of studying viruses hosted by bats.
Article
Immunology
Yuyuan Ma, Junting Jia, Rui Fan, Ying Lu, Xiong Zhao, Yadi Zhong, Jierong Yang, Limin Ma, Yanlin Wang, Maomin Lv, Haiyuan Yang, Lisha Mou, Yifan Dai, Shutang Feng, Jingang Zhang
Summary: This study screened pigs that do not transmit PERV to human cells and investigated their sequence characteristics. It was found that some pigs of the Chinese Wuzhishan minipig inbred line did not transmit PERV, and the pol genes of these pigs were defective at both the genome and transcript levels. This finding is promising for the development of suitable xenotransplantation sources.
FRONTIERS IN IMMUNOLOGY
(2022)