Inhibition of budding/release of porcine endogenous retrovirus

Authors

  • Masumi Abe,

    1. Fifth Biology Section for Microbiology, First Department of Forensic Science, National Research Institute of Police Science, Kashiwa
    Search for more papers by this author
  • Aiko Fukuma,

    1. Fifth Biology Section for Microbiology, First Department of Forensic Science, National Research Institute of Police Science, Kashiwa
    2. Department of Emerging Infectious Diseases, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki
    Search for more papers by this author
  • Rokusuke Yoshikawa,

    1. Laboratory of Signal Transduction, Department of Cell Biology, Institute for Virus Research, Kyoto University, Kyoto, Japan
    Search for more papers by this author
  • Takayuki Miyazawa,

    1. Laboratory of Signal Transduction, Department of Cell Biology, Institute for Virus Research, Kyoto University, Kyoto, Japan
    Search for more papers by this author
  • Jiro Yasuda

    Corresponding author
    1. Fifth Biology Section for Microbiology, First Department of Forensic Science, National Research Institute of Police Science, Kashiwa
    2. Department of Emerging Infectious Diseases, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki
    • Correspondence

      Jiro Yasuda, Department of Emerging Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.

      Tel: +81-95-819-7848; fax: +81-95-819-7848; email: j-yasuda@nagasaki-u.ac.jp

    Search for more papers by this author

Abstract

PERV is integrated into the genome of all pigs. PERV-A and PERV-B are polytropic and can productively infect human cell lines, whereas PERV-C is ecotropic. Recombinant PERV-A/C can infect human cells and exhibits high titer replication. Therefore, use of pigs for human xenotransplantation raises concerns about the risks of transfer of this infectious agent from donors to xenotransplantation recipients. To establish strategies to inhibit PERV production from cells, in the present study, we investigated the mechanism of PERV budding and anti-PERV activity of Tetherin/BST-2. The results showed that DN mutants of WWP-2, Tsg101, and Vps4A/B markedly reduced PERV production in human and porcine cell lines, suggesting that PERV budding uses these cellular factors and the cellular MVB sorting pathway as well as many other retroviruses. Moreover, PERV production was also reduced by human and porcine Tetherin/BST-2. These data are useful for developing strategies to inhibit PERV production and may reduce the risk of PERV infection in xenotransplantation.

Ancillary