Measles virus: immunomodulation and cell tropism as pathogenicity determinants.
As important determinants of measles virus (MV) pathogenicity, the MV glycoproteins play a key role in conferring the cellular tropism of this virus, but also in modulating the activity of immunocompetent cells. Whereas all MV strains are able to use CD150 (SLAM) for binding and entry into target cells, only certain, mainly vaccine, strains, can use both CD46 and CD150. Both molecules are down-regulated from the cell surface and this is brought about by both infection and contact with the MV H protein of strains that are able to interact with these molecules. Whereas down-regulation of CD46 could be linked to enhanced sensitivity to complement-mediated lysis, and may thus represent an attenuation marker for vaccine strains, pathogenetic consequences of CD150 down-regulation are unknown as yet. Although the role of CD150 is not entirely clear, viruses containing a wild-type strain-derived H protein revealed a particular tropism for human dendritic cells in vitro, and replicated well in secondary lymphatic tissues of cotton rats where they were also able to cause immunosuppression, as documented by an impaired proliferative response of lymphocytes ex vivo. Most likely, inhibition of T cell expansion by these cells is brought about by another activity of the MV glycoprotein complex, namely by disrupting a pathway important for S-phase entry of T cells, by a mere surface contact.
Schneider-Schaulies
Sibylle
S
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, Germany. s-s-s@vim.uni-wuerzburg.de
Schneider-Schaulies
Jürgen
J
Niewiesk
Stefan
S
Ter Meulen
Volker
V
D000276:Adjuvants, Immunologic / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D007165:Immunosuppression Therapy; D008457:Measles / Q000276:immunology*; D008459:Measles virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000378:metabolism; D011991:Receptors, Virus / Q000276:immunology; D015398:Signal Transduction; D018523:Tropism
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D018844:Cyclin-Dependent Kinases