Transgenic mice expressing human measles virus (MV) receptor CD46 provide cells exhibiting different permissivities to MV infections

Abstract

We have generated transgenic mice ubiquitously expressing the human receptor for measles virus (MV), CD46 (membrane cofactor protein). Various cell types were isolated from these transgenic mice and analyzed for their ability to support MV replication in vitro. Although MV could enter into all CD46-expressing cells, differential susceptibilities to MV infection were detected depending on the cell type. Cell cultures obtained from transgenic lungs and kidneys were found to be permissive of MV infection, since RNA specific for MV genes was detected and viral particles were released, although at a low level. Similarly to human lymphocytes, activated T and B lymphocytes isolated from transgenic mice could support MV replication; virus could enter, transcribe viral RNA, and produce new infectious particles. When expressing viral proteins, lymphocytes down-regulated CD46 from the surface. Interestingly, while activated T lymphocytes from nontransgenic mice did not support MV infection, activated nontransgenic murine B lymphocytes replicated MV as well as transgenic B lymphocytes, suggesting the use of an alternative virus receptor for entry. In contrast to the previous cell types, murine peritoneal and bone marrow-derived macrophages, regardless of whether they were activated, could not support MV replication. Furthermore, 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 particular cell-type-specific host factors for MV replication in murine cells which may be responsible for the differential permissivity of MV infection.

Infection of human oligodendroglioma cells by a recombinant measles virus expressing enhanced green fluorescent protein

“…A more detailed description of CD46 and SLAM expression in the normal and MV-infected CNS and peripheral tissues is currently in preparation (McQuaid et al, unpublished results). It has been shown that not all cells that are susceptible to MV infection express detectable levels of CD46 (Yanagi et al, 1994;Dunster et al, 1995;Horvat et al, 1996), and SLAM is only constitutively expressed on immature thymocytes, CD45RO high memory T cells, and a proportion of B cells (Sidorenko and Clarke, 1993;Cocks et al, 1995). The mechanism of MV entry into these cells remains unclear and would seem to indicate that other MV receptors may exist on mammalian cells.…”

The relevance of complement to virus biology

“…Human herpesvirus 6 (HHV-6) and measles virus (MV) both use MCP as a cellular receptor, although they utilise different domains of this receptor for binding (Greenstone et al, 2002). Identification of MCP as the receptor for MV has led to the development of a transgenic mouse model that has contributed to in vivo studies of viral pathogenesis (Horvat et al, 1996;Rall et al, 1997). However, the primary MV receptor, signalling lymphocyte-activation molecule (SLAM) (Tatsuo et al, 2000), is not part of the complement system.…”

Evolution of Cell Recognition by Viruses: A Source of Biological Novelty with Medical Implications

“…Human parainfluenza virus 1, 3 Sialic acid residues on gangliosides glycolipids (Suzuki et al, 2001) Measles virus CD46 (Dorig et al, 1993;Naniche et al, 1993;Schneider-Schaulies et al, 1995;Horvat et al, 1996;Buckland and Wild, 1997;Buchholz et al, 1997;Niewiesk et al, 1997); SLAM (Tatsuo et al, 2000b)…”