Measles virus vaccine attenuation: suboptimal infection of lymphatic tissue and tropism alteration.
The mechanisms of measles virus (MV) vaccine attenuation are insufficiently characterized. Because the Edmonston vaccine strain can enter cells through CD46 in addition to the primary MV receptor signaling lymphocyte activation molecule (SLAM or CD150), we asked whether and how its tropism is altered. In human tonsillar tissue, this vaccine strain infects naive (CD45RA(+)CD62L(+)) T lymphocytes, which express SLAM very infrequently, with much higher efficiency than do wild-type strains. By contrast, it infects B lymphocytes, macrophages, and NK cells with significantly lower efficiencies than those of wild-type strains. Infection levels by wild-type strains correlate with the frequency of SLAM expression and are highest in B cells, which are 40%-55% infected. SLAM-expressing T cells are more readily infected by all MV strains than are SLAM-expressing B cells. Thus, vaccine attenuation may be caused by tropism alteration in combination with suboptimal replication.
Condack
Cristian
C
Laboratory of Molecular and Cellular Biophysics, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
Grivel
Jean-Charles
JC
Devaux
Patricia
P
Margolis
Leonid
L
Cattaneo
Roberto
R
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology; D002144:Callithrix; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006801:Humans; D007156:Immunologic Memory; D007694:Killer Cells, Natural / Q000378:metabolism / Q000821:virology; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D008457:Measles / Q000821:virology*; D008458:Measles Vaccine / Q000378:metabolism*; D008459:Measles virus / Q000502:physiology*; D051916:Membrane Cofactor Protein / Q000378:metabolism; D014066:Palatine Tonsil / Q000378:metabolism / Q000821:virology; D011956:Receptors, Cell Surface / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D014613:Vaccines, Attenuated / Q000378:metabolism; D014709:Vero Cells; D014779:Virus Replication
D015703:Antigens, CD; D008458:Measles Vaccine; D051916:Membrane Cofactor Protein; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; C000604059:SLAMF1 protein, human; D014613:Vaccines, Attenuated; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1