TY - JOUR
T1 - Measles virus vaccine attenuation
T2 - Suboptimal infection of lymphatic tissue and tropism alteration
AU - Condack, Cristian
AU - Grivel, Jean Charles
AU - Devaux, Patricia
AU - Margolis, Leonid
AU - Cattaneo, Roberto
N1 - Funding Information:
Received 22 November 2006; accepted 6 March 2007; electronically published 29 June 2007. Potential conflicts of interest: none reported. Financial support: National Institute of Child Health and Human Development intramural program (support to C.C., J-C.G., and L.M.); National Institutes of Health (grants R01 CA90636 and R01 AI57761 to P.D. and R.C.). Reprints or correspondence: Dr. Jean-Charles Grivel, NIH Bldg. 10, Rm. 9D58, 10 Center Dr., Bethesda, MD 20892 (grigri@helix.nih.gov).
PY - 2007/8/15
Y1 - 2007/8/15
N2 - 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.
AB - 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.
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U2 - 10.1086/519689
DO - 10.1086/519689
M3 - Article
C2 - 17624839
AN - SCOPUS:34547633342
SN - 0022-1899
VL - 196
SP - 541
EP - 549
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 4
ER -