CD46- and CD150-independent endothelial cell infection with wild-type measles viruses

Abstract

Measles virus (MV) infects endothelial cells of the skin, the brain and other organs during acute or persistent infections. Endothelial cells are supposed to play an important role in virus spread from the blood stream to surrounding tissues. CD46 and CD150 (signalling lymphocytic activation molecule, SLAM) have been described as cellular receptors for certain MV strains. We found that human umbilical vein and brain microvascular endothelial cells (HUVECs and HBMECs) were CD46-positive, but did not express SLAM. Wild-type MV strains, which do not use CD46 as a receptor at the surface of transfected Chinese hamster ovary cells, infected HUVECs and HBMECs to varying extents in a strain-dependent way. This infection was not inhibited by antibodies to CD46. These data suggest the presence of an additional unidentified receptor for MV uptake and spread in human endothelial cells. INTRODUCTIONAfter acute infection of the upper respiratory tract, measles virus (MV) is rapidly transported to draining lymph nodes forming giant cells in the reticulo-endothelial system. MV then establishes a systemic infection and spreads to different organs, including the skin. In these organs, virus replicates primarily in endothelial cells (ECs), epithelial cells and monocytes/macrophages (Griffin & Bellini, 1996). ECs of dermal capillaries (Kimura et al., 1975) and small vessels throughout the body show clear evidence of MV infection. This appears to play a central role in pathogenesis, leading to changes in the skin, conjunctivae, mucous membranes and the brain (Cosby & Brankin, 1995), accompanied by vascular dilatation, increased vascular permeability, mononuclear cell infiltration and infection of surrounding tissues. In rare cases, the EC infection may extend to a severe haemorrhagic infection with confluent haemorrhagic skin eruptions and intravascular coagulopathy, so-called haemorrhagic or black measles. Brain ECs and capillary endothelium of lymph nodes and the thymus have been found to be infected in fatal cases of acute measles (Esolen et al., 1995; Moench et al., 1988). In subacute sclerosing panencephalitis (SSPE) patients, brain ECs appear to be infected in addition to various neural cells (Allen et al., 1996;Isaacson et al., 1996;Kirk et al., 1991).Following the identification of CD46 as a receptor for MV vaccine and laboratory strains (Dörig et al., 1993;Naniche et al., 1993a), evidence has accumulated that many wildtype isolates do not use CD46 as a receptor. Recently, the signalling lymphocytic activation molecule (SLAM, CD150) has been identified as a common receptor interacting with MV vaccine as well as wild-type strains (Erlenhoefer et al., 2001(Erlenhoefer et al., , 2002Hsu et al., 2001; Ono et al., 2001a, b;Tatsuo et al., 2000). SLAM is expressed on human B cell lines, primary activated B and T cells, memory cells and activated monocytes and monocyte-derived dendritic cells (Cocks et al., 1995;Minagawa et al., 2001;Ohgimoto et al., 2001;Polacino et al., 1996;Punnonen et al., 1997), and its usage as a receptor c...

Blood-brain barrier invasion by group B Streptococcus depends upon proper cell-surface anchoring of lipoteichoic acid

“…The hBMEC line has been shown to express TLR2 by RT-PCR analysis (24). In our earlier microarray analysis of hBMECs (14), we found that the gene for the chemokine IL-8, a common target of TLR/NF-κB-mediated activation, was the single most strongly induced gene following GBS stimulation (> 60-fold upregulation), a finding confirmed by ELISA for IL-8 protein.…”

Contributions of Matrix and Large Protein Genes of the Measles Virus Edmonston Strain to Growth in Cultured Cells as Revealed by Recombinant Viruses

“…Takeuchi et al also reported that there was no sequence difference in the H gene between MV strains isolated in B95a and in Vero cells from the same measles patient, although they exhibited distinct tropisms (43). We and others have previously demonstrated the presence of SLAM-and CD46-independent cell entry of MV (1,12). However, as its efficiency is 2 to 3 log units lower than that of SLAM-or CD46-dependent entry, this inefficient entry can only partly account for the above observations.…”

A Human Lung Carcinoma Cell Line Supports Efficient Measles Virus Growth and Syncytium Formation via a SLAM- and CD46-Independent Mechanism

“…Although studies have shown a low level of SLAM-independent infection by wt MV in various cell lines (the efficiency was 100 to 1,000 times lower than that using SLAM), this type of infection usually does not produce syncytia in infected cells (9). Exceptions are primary cultures of human small airway epithelial cells and endothelial cells (1,43). wt MV induced syncytia in these cells via a SLAM-independent mechanism (1,43).…”