Prolonged persistence of measles virus RNA is characteristic of primary infection dynamics

Wen Hsuan W. Lin, Roger D. Kouyos, Robert J. Adams, Bryan T. Grenfell, Diane E. Griffin

Research output: Contribution to journalArticle

Abstract

Measles virus (MeV) is the poster child for acute infection followed by lifelong immunity. However, recent work shows the presence of MeV RNA in multiple sites for up to 3 mo after infection in a proportion of infected children. Here, we use experimental infection of rhesus macaques to show that prolonged RNA presence is characteristic of primary infection. We found that viral RNA persisted in the blood, respiratory tract, or lymph nodes four to five times longer than the infectious virus and that the clearance of MeV RNA from blood happened in three phases: rapid decline coincident with clearance of infectious virus, a rebound phase with increases up to 10-fold, and a phase of slow decrease to undetectable levels. To examine the effect of individual host immune factors on MeV load dynamics further, we developed a mathematical model that expressed viral replication and elimination in terms of the strength of MeV-specific T-cell responses, antibody responses, target cell limitations, and immunosuppressive activity of regulatory T cells. Based on the model, we demonstrate that viral dynamics, although initially regulated by T cells, require antibody to eliminate viral RNA. These results have profound consequences for our view of acute viral infections, the development of prolonged immunity, and, potentially, viral evolution.

Original languageEnglish (US)
Pages (from-to)14989-14994
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number37
DOIs
StatePublished - Sep 11 2012

Keywords

  • Immune responses
  • Virus clearance
  • Within-host modeling

ASJC Scopus subject areas

  • General

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