TRANSGENIC MICE EXPRESSING HUMAN MEASLES-VIRUS (MV) RECEPTOR CD46 PROVIDE CELLS EXHIBITING DIFFERENT PERMISSIVITIES TO MV INFECTION

We have generated transgenic mice ubiquitously expressing the human re ceptor for measles virus (MV), CD46 (membrane cofactor protein), Vario us cell types were isolated from these transgenic mice acid analyzed f or their ability to support MV replication in vitro, Although MV could enter into all CD46-expressing cells, differential susceptibilities t o MV infection were detected depending on the cell type, Cell cultures obtained from transgenic lungs and kidneys were found to be permissiv e of MV infection, since RNA specific for MV genes was detected and vi ral particles were released, although at a low level, Similarly to hum an lymphocytes, activated T and B lymphocytes isolated from transgenic mice could support MV replication; virus could enter, transcribe vira l RNA, and produce new infectious particles, When expressing viral pro teins, lymphocytes down-regulated CD46 from the surface, Interestingly , while activated T lymphocytes from nontransgenic mice did not suppor t MV infection, activated nontransgenic murine B Lymphocytes replicate d MV as well as transgenic B lymphocytes, suggesting the use of an alt ernative virus receptor for entry. In contrast to the previous cell ty pes, murine peritoneal and bone marrow derived macrophages, regardless of whether they were activated, could not support MV replication. Fur thermore, although MV entered into macrophages and virus-specific RNA transcription occurred, no virus protein or infectious virus particles could be detected, These results show the importance of the particula r cell-type-specific host factors for MV replication in murine cells w hich may be responsible for the differential permissivity of MV infect ion.