title: CD46 transgene expression in pig peripheral blood mononuclear cells does not alter their susceptibility to measles virus or their capacity to downregulate endogenous and transgenic CD46.
abstract: CD46 (or membrane cofactor protein) protects autologous cells from complement-mediated lysis and has been expressed as a transgene in pigs to overcome complement-mediated hyperacute rejection of porcine organs upon transplantation into primates. Since CD46 has been identified as a receptor for measles virus (MV), the susceptibility of CD46-transgenic (tg) pig peripheral blood mononuclear cells (PBMC) to infection with MV strains which do and do not use CD46 as receptor was investigated. Surprisingly, it was found that MV vaccine strains (e.g. Edmonston) bound to tg as well as non-tg pig PBMC. Phytohaemagglutinin-stimulated CD46-tg and non-tg pig PBMC were equally well infected with MV vaccine strains irrespective of CD46 expression. Upon infection, tg CD46 was downregulated from the cell surface. In contrast, the binding capacity for MV wild-type strains to pig and human PBMC was low, irrespective of CD46 expression. These MV strains did not infect tg or non-tg pig cells. Expression of endogenous pig CD46 was detected with polyclonal sera against human CD46. After infection of pig PBMC with MV strain Edmonston, endogenous pig CD46 was also downregulated. This suggests an interaction between MV Edmonston and pig CD46. However, polyclonal CD46 sera did not inhibit infection with MV Edmonston indicating that CD46 may not exclusively act as a receptor for MV on these cells. Interestingly, similar results were observed using human PBMC. Data suggest that CD46 downregulation after interaction with MV may also occur in porcine organs which express endogenous and/or human CD46 as a means of protection against complement-mediated damage.
authors.affiliation: Institut für Virologie und Immunbiologie, Versbacher Str. 7, D-97078 Würzburg, Germany. jss@vim.uni-wuerzburg.de
authors.forename: J
authors.initials: J
authors.lastname: Schneider-Schaulies
authors.forename: M J
authors.initials: MJ
authors.lastname: Martin
authors.forename: J S
authors.initials: JS
authors.lastname: Logan
authors.forename: R
authors.initials: R
authors.lastname: Firsching
authors.forename: V
authors.initials: V
authors.lastname: ter Meulen
authors.forename: L E
authors.initials: LE
authors.lastname: Diamond
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D015536:Down-Regulation; D015870:Gene Expression; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D008458:Measles Vaccine; D008459:Measles virus / Q000378:metabolism / Q000502:physiology*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D013552:Swine; D019076:Transgenes
chemical_list: D015703:Antigens, CD; C497857:CD46 protein, human; D008458:Measles Vaccine; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011991:Receptors, Virus