The haemagglutinin protein is an important determinant of measles virus tropism for dendritic cells in vitro.
Recombinant measles viruses (MV) in which the authentic glycoprotein genes encoding the fusion and the haemagglutinin (H) proteins of the Edmonston (ED) vaccine strains were swapped singly or doubly for the corresponding genes of a lymphotropic MV wild-type virus (strain WTF) were used previously to investigate MV tropism in cell lines in tissue culture. When these recombinants and their parental strains, the molecular ED-based clone (ED-tag) and WTF, were used to infect cotton rats, only viruses expressing the MV WTF H protein replicated in secondary lymphatic tissues and caused significant immunosuppression. In vitro, viruses containing the ED H protein revealed a tropism for human peripheral blood lymphocytes as documented by enhanced binding and virus production, whereas those containing the WTF H protein replicated well in monocyte-derived dendritic cells (Mo-DC). This did not correlate with more efficient binding of these viruses to DC, but with an enhancement of uptake, virus spread, accumulation of viral antigens and virus production. Thus, replacement of the ED H protein with WTF H protein was sufficient to confer the DC tropism of WTF to ED-tag in vitro. This study suggests that the MV H protein plays an important role in determining cell tropism to immune cells and this may play an important role in the induction of immunosuppression in vivo.
Ohgimoto
Shinji
S
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, D-97078 Würzburg, Germany1.
Ohgimoto
Kaori
K
The Second Department of Internal Medicine, School of Medicine, Mie University, 2-174 Edobashi, Tsu-City, Mie, Japan4.|Institute for Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, D-97078 Würzburg, Germany1.
Niewiesk
Stefan
S
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, D-97078 Würzburg, Germany1.
Klagge
Ingo M
IM
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, D-97078 Würzburg, Germany1.
Pfeuffer
Joanna
J
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, D-97078 Würzburg, Germany1.
Johnston
Ian C D
ICD
Miltenyi Biotech GmbH, 51429 Bergisch-Gladbach, Germany2.
Schneider-Schaulies
Jürgen
J
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, D-97078 Würzburg, Germany1.
Weidmann
Armin
A
Emory University, Yerkes Vaccine Center, 954 Gatewood Road, Atlanta, GA 30322, USA3.
Ter Meulen
Volker
V
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, D-97078 Würzburg, Germany1.
Schneider-Schaulies
Sibylle
S
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, D-97078 Würzburg, Germany1.
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral; D003713:Dendritic Cells / Q000821:virology*; D004195:Disease Models, Animal; D006389:Hemagglutinins, Viral / Q000032:analysis*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008198:Lymph Nodes / Q000821:virology; D008457:Measles / Q000821:virology*; D008459:Measles virus / Q000235:genetics / Q000472:pathogenicity*; D011995:Recombination, Genetic; D016205:Sigmodontinae; D013154:Spleen / Q000821:virology; D013997:Time Factors
D006389:Hemagglutinins, Viral