Measles immune suppression: lessons from the Macaque Model

Rory D. de Vries, Stephen McQuaid, Geert van Amerongen, Selma Yüksel, R. Joyce Verburgh, Albert D.M.E. Osterhaus, W. Paul Duprex, Rik L. de Swart

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Measles remains a significant childhood disease, and is associated with a transient immune suppression. Paradoxically, measles virus (MV) infection also induces robust MV-specific immune responses. Current hypotheses for the mechanism underlying measles immune suppression focus on functional impairment of lymphocytes or antigen-presenting cells, caused by infection with or exposure to MV. We have generated stable recombinant MVs that express enhanced green fluorescent protein, and remain virulent in non-human primates. By performing a comprehensive study of virological, immunological, hematological and histopathological observations made in animals euthanized at different time points after MV infection, we developed a model explaining measles immune suppression which fits with the "measles paradox". Here we show that MV preferentially infects CD45RA - memory T-lymphocytes and follicular B-lymphocytes, resulting in high infection levels in these populations. After the peak of viremia MV-infected lymphocytes were cleared within days, followed by immune activation and lymph node enlargement. During this period tuberculin-specific T-lymphocyte responses disappeared, whilst strong MV-specific T-lymphocyte responses emerged. Histopathological analysis of lymphoid tissues showed lymphocyte depletion in the B- and T-cell areas in the absence of apoptotic cells, paralleled by infiltration of T-lymphocytes into B-cell follicles and reappearance of proliferating cells. Our findings indicate an immune-mediated clearance of MV-infected CD45RA - memory T-lymphocytes and follicular B-lymphocytes, which causes temporary immunological amnesia. The rapid oligoclonal expansion of MV-specific lymphocytes and bystander cells masks this depletion, explaining the short duration of measles lymphopenia yet long duration of immune suppression. © 2012 de Vries et al.
Original languageEnglish
Article numbere1002885
JournalPLoS Pathogens
Volume8
Issue number8
DOIs
Publication statusPublished - Aug 2012

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Fingerprint Dive into the research topics of 'Measles immune suppression: lessons from the Macaque Model'. Together they form a unique fingerprint.

  • Cite this

    de Vries, R. D., McQuaid, S., van Amerongen, G., Yüksel, S., Verburgh, R. J., Osterhaus, A. D. M. E., Duprex, W. P., & de Swart, R. L. (2012). Measles immune suppression: lessons from the Macaque Model. PLoS Pathogens, 8(8), [e1002885]. https://doi.org/10.1371/journal.ppat.1002885