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

CD46 (or membrane cofactor protein) protects autologous cells from compleme nt-mediated lysis and has been expressed as a transgene in pigs to overcome complement-mediated hyperacute rejection of porcine organs upon transplant ation into primates. Since CD46 has been identified as a receptor for measl es virus (MV), the susceptibility of CD46-transgenic (tg) pig peripheral bl ood mononuclear cells (PBMC) to infection with MV strains which do and do n ot use CD46 as receptor was investigated. Surprisingly, it was found that M V 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 wel l infected with MV vaccine strains irrespective of CD46 expression, Upon in fection, 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, ir respective 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 Edmonst on, endogenous pig CD46 was also downregulated, This suggests an interactio n between MV Edmonston and pig CD46. However, polyclonal CD46 sera did not inhibit infection with MV Edmonston indicating that CD46 may not exclusivel y act as a receptor for MV on these cells. Interestingly, similar results w ere observed using human PBMC, Data suggest that CD46 downregulation after interaction with MV may also occur in porcine organs which express endogeno us and/or human CD46 as a means of protection against complement-mediated d amage.