Role of CD46 in measles virus infection in CD46 transgenic mice.
The susceptibility of CD46 (human membrane cofactor protein) transgenic mice to measles virus (MV) infection was investigated. Cell cultures (lung and kidney) established from transgenic and control mice showed that although both could be infected only those from the CD46+ mice gave fusion. A complete round of replication with the release of infectious virus was detected exclusively in the transgenic cell cultures whose permissiveness to MV was markedly less than that of Vero cells. The ability of MV to replicate in vivo in mice was studied using both vaccine and laboratory-adapted wild-type strains of virus. After intraperitoneal and intranasal inoculations of transgenic mice, virus replication could not be detected. In contrast intracerebral inoculation induced infection in both transgenic and nontransgenic mice. Our results from in vitro infection studies support the hypothesis that CD46 is a major host cell factor involved in the MV-induced fusion process and MV entry. The studies further indicate that MV tropism is not governed solely by the expression of the CD46 gene and that the high efficiency of the replicative cycles characteristic of fully permissive host cells requires additional factors, which are lacking in both transgenic and nontransgenic mice.
Blixenkrone-Møller
M
M
Immunité et Vaccination, Ex-Bâtiment Institut Pasteur de Lyon, Avenue Tony Garnier, Lyon Cedex 07, 69365, France. MBM@KVL.DK
Bernard
A
A
Bencsik
A
A
Sixt
N
N
Diamond
L E
LE
Logan
J S
JS
Wild
T F
TF
D000281:Administration, Intranasal; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000502:physiology*; D000956:Antigens, Viral / Q000302:isolation & purification; D001483:Base Sequence; D001921:Brain; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007267:Injections; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000821:virology; D008168:Lung / Q000821:virology; D008297:Male; D008457:Measles / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D008459:Measles virus / Q000276:immunology* / Q000472:pathogenicity* / Q000502:physiology; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014779:Virus Replication
D015703:Antigens, CD; D000956:Antigens, Viral; C497857:CD46 protein, human; D017931:DNA Primers; C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D012367:RNA, Viral