title: Inhibition of budding/release of porcine endogenous retrovirus.
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.
authors.affiliation: Fifth Biology Section for Microbiology, First Department of Forensic Science, National Research Institute of Police Science, Kashiwa, 277-0882.
authors.forename: Masumi
authors.initials: M
authors.lastname: Abe
authors.forename: Aiko
authors.initials: A
authors.lastname: Fukuma
authors.forename: Rokusuke
authors.initials: R
authors.lastname: Yoshikawa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Miyazawa
authors.forename: Jiro
authors.initials: J
authors.lastname: Yasuda
mesh_terms: D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D020077:Endogenous Retroviruses / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D011991:Receptors, Virus / Q000378:metabolism; D012192:Retroviridae Infections / Q000209:etiology / Q000378:metabolism / Q000662:veterinary* / Q000821:virology*; D013552:Swine; D013553:Swine Diseases / Q000378:metabolism / Q000821:virology*; D014183:Transplantation, Heterologous / Q000009:adverse effects; D057074:Virus Release; D014779:Virus Replication
chemical_list: D011991:Receptors, Virus
keywords: Tetherin/BST-2; endosomal sorting complexes required for transport (ESCRT); porcine endogenous retrovirus (PERV); retrovirus