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 (E D) vaccine strains were swapped singly or doubly for the corresponding gene s of a lymphotropic MV wild-type virus (strain WTF) were used previously to investigate MV tropism in cell lines in tissue culture. When these recombi nants 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 i mmunosuppression, In vitro, viruses containing the ED H protein revealed a tropism for human peripheral blood lymphocytes as documented by enhanced bi nding and virus production, whereas those containing the WTF H protein repl icated well in monocyte-derived dendritic cells (Mo-DC), This did not corre late with more efficient binding of these viruses to DC, but with an enhanc ement of uptake, virus spread, accumulation of viral antigens and virus pro duction. Thus, replacement of the ED H protein with WTF H protein was suffi cient to confer the DC tropism of WTF to ED-tag in vitro, This study sugges ts that the MV H protein plays an important role in determining cell tropis m to immune cells and this may play an important role in the induction of i mmunosuppression in vivo.