Modeling the measles paradox reveals the importance of cellular immunity in regulating viral clearance

• DOI: 10.1371/journal.ppat.1007493
• Publication Date: 2018-12-28T18:24:26Z
• Authors: Sinead E. Morris; Andrew J. Yates; Rik L. de Swart; Rory D. de Vries; Michael J. Mina; Ashley N. Nelson; Wen-Hsuan W. Lin; Roger D. Kouyos; Diane E. Griffin; Bryan T. Grenfell
• Keywords: Immunosuppression; Morbillivirus; Canine distemper

Measles virus (MV) is a highly contagious member of the Morbillivirus genus that remains major cause childhood mortality worldwide. Although infection induces strong MV-specific immune response clears viral load and confers lifelong immunity, transient immunosuppression can also occur, leaving host vulnerable to colonization from secondary pathogens. This apparent contradiction clearance in face underlies what often referred as 'measles paradox', poorly understood. To explore mechanistic basis underlying measles paradox, identify key factors driving clearance, we return previously published dataset MV rhesus macaques. These data include virological immunological information enable us fit mathematical model describing how interacts with system. In particular, our incorporates target cell depletion through cells-a hallmark pathology has been neglected previous models. We find captures well, both activation are required explain overall dynamics. Furthermore, by simulating conditions increased availability suppressed cellular show latter causes greater increases delays clearance. Overall, this signals more dominant role for immunity resolving acute infection. Interestingly, contrasting dynamics dominated when fitness increased. may have wider implications animal morbilliviruses, such canine distemper (CDV), fatal their natural hosts. knowledge work represents first fully calibrated within-host and, broadly, provides new platform which complex mechanisms