A Single Amino Acid Change in the Hemagglutinin Protein of Measles Virus Determines Its Ability To Bind CD46 and Reveals Another Receptor on Marmoset B Cells

Abstract

This paper provides evidence for a measles virus receptor other than CD46 on transformed marmoset and human B cells. We first showed that most tissues of marmosets are missing the SCR1 domain of CD46, which is essential for the binding of Edmonston measles virus, a laboratory strain that has been propagated in Vero monkey kidney cells. In spite of this deletion, the common marmoset was shown to be susceptible to infections by wild-type isolates of measles virus, although they did not support Edmonston measles virus production. As one would expect from these results, measles virus could not be propagated in owl monkey or marmoset kidney cell lines, but surprisingly, both a wild-type isolate (Montefiore 89) and the Edmonston laboratory strain of measles virus grew efficiently in B95-8 marmoset B cells. In addition, antibodies directed against CD46 had no effect on wild-type infections of marmoset B cells and only partially inhibited the replication of the Edmonston laboratory strain in the same cells. A direct binding assay with insect cells expressing the hemagglutinin (H) proteins of either the Edmonston or Montefiore 89 measles virus strains was used to probe the receptors on these B cells. Insect cells expressing Edmonston H but not the wild-type H bound to rodent cells with CD46 on their surface. On the other hand, both the Montefiore 89 H and Edmonston H proteins adhered to marmoset and human B cells. Most wild-type H proteins have asparagine residues at position 481 and can be converted to a CD46-binding phenotype by replacement of the residue with tyrosine. Similarly, the Edmonston H protein did not bind CD46 when its Tyr481 was converted to asparagine. However, this mutation did not affect the ability of Edmonston H to bind marmoset and human B cells. The preceding results provide evidence, through the use of a direct binding assay, that a second receptor for measles virus is present on primate B cells.

Morbillivirus Receptors and Tropism: Multiple Pathways for Infection

“…From these observations, it had been postulated that B-cell line-isolated strains do not use the ubiquitously expressed CD46 but utilize another molecule as a receptor (Lecouturier et al, 1996;Buckland and Wild, 1997;Bartz et al, 1998;Hsu et al, 1998;Tanaka et al, 1998;Tatsuo et al, 2000a). Tatsuo et al (2000b) performed a screening of a cDNA library of B95a cells, in which a non-susceptible human kidney cell line, 293T, was transfected with the cDNA library and then screened with a vesicular stomatitis virus pseudotype bearing the H protein of MeV isolated from B-cells and F protein from the Edmonston strain.…”

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

“…Although wild-type MV interacts with SLAM with high affinity, it can also interact with CD46 with low affinity (Masse et al, 2002). A single amino acid replacement in the surface hemagglutinin of the MV envelope determines the ability of the virus to bind CD46 with high affinity (Hsu et al, 1998). Additional receptors may be involved in MV infection (Hashimoto et al, 2002;Oldstone et al, 2002).…”

Measles Virus Receptor SLAM (CD150)

“…The Edmonston and Vero cell isolated strains are capable of infecting any CD46 ϩ primate cell lines. On the other hand, B cell isolated strains grow in a restricted number of B and T cell lines and phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMC), but not in other CD46 ϩ cell lines (Schneider-Schaulies et al, 1995b;Lecouturier et al, 1996;Hsu et al, 1998;Tanaka et al, 1998;Tatsuo et al, 2000a). Furthermore, the Edmonston strain causes hemadsorption with monkey red blood cells (which express CD46, unlike human red blood cells) and CD46 downregulation from the surface of the infected cells, whereas B cell isolated strains do not (Saito et al, 1992;Naniche et al, 1993b;Schneider-Schaulies et al, 1995a;Lecouturier et al, 1996).…”

“…MV has two envelope glycoproteins, the hemagglutinin (H) and fusion (F) protein, mediating receptor binding and membrane fusion, respectively (Griffin, 2001). Several studies provided evidence that the H protein of the Edmonston strain, but not of B cell isolated strains, interacts with CD46 (Lecouturier et al, 1996;Hsu et al, 1998;Tanaka et al, 1998), suggesting the presence of another receptor for B cell isolated strains. Others, however, argued that B cell isolated strains can enter cells using CD46, but fail to replicate in nonlymphoid cells (Schneider-Schaulies et al, 1995b;Manchester et al, 2000).…”