Porcine endogenous retroviruses PERV A and A/C recombinant are insensitive to a range of divergent mammalian TRIM5alpha proteins including human TRIM5alpha.
The potential risk of cross-species transmission of porcine endogenous retroviruses (PERV) to humans has slowed the development of xenotransplantation, using pigs as organ donors. Here, we show that PERVs are insensitive to restriction by divergent TRIM5alpha molecules despite the fact that they strongly restrict a variety of divergent lentiviruses. We also show that the human PERV A/C recombinant clone 14/220 reverse transcribes with increased efficiency in human cells, leading to significantly higher infectivity. We conclude that xenotransplantation studies should consider the danger of highly infectious TRIM5alpha-insensitive human-tropic PERV recombinants.
Wood
Andrew
A
MRC Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, 46 Cleveland Street, London W1T 4JF, UK.
Webb
Benjamin L J
BLJ
MRC Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, 46 Cleveland Street, London W1T 4JF, UK.
Bartosch
Birke
B
Université de Lyon, (UCB-Lyon1), IFR128, Lyon, F-69007, France; INSERM, U758, Lyon, F-69007, France; Ecole Normale Supérieure de Lyon, Lyon, F-69007, France.
Schaller
Torsten
T
MRC Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, 46 Cleveland Street, London W1T 4JF, UK.
Takeuchi
Yasuhiro
Y
MRC Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, 46 Cleveland Street, London W1T 4JF, UK.
Towers
Greg J
GJ
MRC Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, 46 Cleveland Street, London W1T 4JF, UK.
D000595:Amino Acid Sequence; D000818:Animals; D000090103:Antiviral Restriction Factors; D002213:Capsid / Q000737:chemistry / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D002460:Cell Line; D020077:Endogenous Retroviruses / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D011995:Recombination, Genetic; D048348:Reverse Transcription; D013552:Swine / Q000821:virology*; D014183:Transplantation, Heterologous; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D011506:Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; C482587:TRIM5(alpha) protein, rhesus monkey; D044767:Ubiquitin-Protein Ligases