SLAM (CD150)-Independent Measles Virus Entry as Revealed by Recombinant Virus Expressing Green Fluorescent Protein

Abstract

IC323-EGFP infection of SLAM-negative cells. This infection occurred under conditions in which entry via endocytosis was inhibited. These results indicate that MV can infect a variety of cells, albeit with a low efficiency, by using an as yet unidentified receptor(s) other than SLAM or CD46, in part explaining the observed MV infection of SLAM-negative cells in vivo.Measles virus (MV) is an enveloped virus of the Morbillivirus genus in the Paramyxoviridae family and has a linear, nonsegmented, negative-strand RNA genome with two envelope glycoproteins, the hemagglutinin (H) and fusion (F) proteins (12). Despite the development of effective live vaccines, measles remains a significant cause of infant mortality worldwide, mainly due to secondary infections caused by MV-induced immunosuppression (12).Vaccine strains of MV such as the Edmonston strain use human CD46 as a cellular receptor (9, 25). Since CD46 is expressed on all nucleated human cells (19), vaccine strains of MV can infect almost any human cell line. In contrast, wildtype strains of MV isolated in the marmoset B-cell line B95a or human B-cell lines are usually unable to use CD46 as a receptor (6,13,17,18,36,37,46,47). Recently, we have demonstrated that signaling lymphocyte activation molecule (SLAM; also known as CD150) acts as a cellular receptor for both vaccine and wild-type strains of MV (48). SLAM is a costimulatory molecule in lymphocyte activation (7), and its expression is restricted to activated T and B lymphocytes, immature thymocytes (7, 41), mature dendritic cells (26), and activated monocytes (23), nicely explaining the tropism of MV as well as the lymphopenia and immunosuppression observed in MV infection. We have also reported that viruses obtained from clinical specimens (throat swabs of measles patients) use SLAM but not CD46 as a receptor (28). Previous histopathological studies in vivo, however, have revealed that in addition to infecting SLAM-positive cells of the immune system, MV also infects endothelial (11, 15, 16, 21, 24), epithelial (21, 24, 44), and neuronal cells (3,24,40), none of which have been shown to express SLAM (7, 41). Thus, the in vivo receptor usage of MV remains to be determined.Reverse genetics technology has enabled us to study a number of important problems concerning virus replication and pathogenesis. As for MV, the rescue of the Edmonston strain from cloned DNA was developed in 1995 (32), providing us with many insights into MV biology (10,30,31,35,49,50). However, since the vaccine strain does not exhibit pathogenicity in experimentally infected monkeys (1, 17), results obtained with it may not be applicable to clinical problems in vivo. Recently, Takeda et al. have successfully developed the rescue system of a wild-type MV strain that could reproduce the natural course of MV pathology in monkeys, opening the way to molecularly dissecting the pathogenesis of MV infection at the level of viral genomes (45).In this study, we examined MV entry into SLAM-negative cells. To facilitate the analysis, we recove...

Infection of lymphoid tissues in the macaque upper respiratory tract contributes to the emergence of transmissible measles virus

“…Two recombinant fluorescent and pathogenic rMV strains, rMV IC323 EGFP and rMV KS EGFP, which have been used previously to study the pathogenesis of MV in the macaque (de Swart et al, 2007;de Vries et al, 2010ade Vries et al, , 2012Lemon et al, 2011) (Hashimoto et al, 2002;Kobune et al, 1990). We did not observe strain-or host speciesspecific differences in the studies described in this paper.…”

Cooperation between different RNA virus genomes produces a new phenotype

“…MV can infect various cultured cells independent of known receptors albeit at low efficiencies (100-to 1000-fold lower than that of SLAM-dependent infection) 19 . This inefficient infection has been postulated to account for MV infection of neurons in human patients 20 .…”

“…Recombinant viruses based on the IC-B strain 19 were recovered as described previously 21 . The M gene was replaced by the Edmonston strain M gene to facilitate virus particle formation 22 .…”

Human Langerhans cells capture measles virus through Langerin and present viral antigens to CD4+ T cells but are incapable of cross‐presentation

“…The wild-type MV strain WTF [51], the laboratory-adapted MV strain Edmonston B, the recombinant pathogenic MV strain IC323-eGFP [52] and the recombinant attenuated strain Edmonston-eGFP [53] were propagated on Vero-CD150 cells and purified by discontinuous sucrose gradient ultracentrifugation. Purified MV strains were UV-inactivated (30 min, 15 W, 312 nm, 1.5 J/cm 2 ).…”