Identification of receptors for pig endogenous retrovirus.
Xenotransplantation of porcine tissues has the potential to treat a wide variety of major health problems including organ failure and diabetes. Balanced against the potential benefits of xenotransplantation, however, is the risk of human infection with a porcine microorganism. In particular, the transmission of porcine endogenous retrovirus (PERV) is a major concern [Chapman, L. E. & Bloom, E. T. (2001) J. Am. Med. Assoc. 285, 2304-2306]. Here we report the identification of two, sequence-related, human proteins that act as receptors for PERV-A, encoded by genes located on chromosomes 8 and 17. We also describe homologs from baboon and porcine cells that also are active as receptors. Conversely, activity could not be demonstrated with a syntenic murine receptor homolog. Sequence analysis indicates that PERV-A receptors [human PERV-A receptor (HuPAR)-1, HuPAR-2, baboon PERV-A receptor 2, and porcine PERV-A receptor] are multiple membrane-spanning proteins similar to receptors for other gammaretroviruses. Expression is widespread in human tissues including peripheral blood mononuclear cells, but their biological functions are unknown. The identification of the PERV-A receptors opens avenues of research necessary for a more complete assessment of the retroviral risks of pig to human xenotransplantation.
Ericsson
Thomas A
TA
Immerge BioTherapeutics, Inc., 300 Technology Square, Cambridge, MA 02139, USA.
Takeuchi
Yasuhiro
Y
Templin
Christian
C
Quinn
Gary
G
Farhadian
Shelli F
SF
Wood
James C
JC
Oldmixon
Beth A
BA
Suling
Kristen M
KM
Ishii
Jennifer K
JK
Kitagawa
Yoshinori
Y
Miyazawa
Takayuki
T
Salomon
Daniel R
DR
Weiss
Robin A
RA
Patience
Clive
C
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D020077:Endogenous Retroviruses / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011991:Receptors, Virus / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013552:Swine
D017931:DNA Primers; D011991:Receptors, Virus