Atenuação do vírus vacinal do sarampo: infecção sub-ótima do tecido linfático e alteração do tropismo

Abstract

The mechanisms of measles virus (MV) vaccine attenuation are insufficiently characterized. Because the vaccine strain can enter cells through CD46 in addition to the primary MV receptor signaling lymphocyte activation molecule (SLAM, 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 Tcells 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.