Mucosal host immune response predicts the severity and duration of herpes simplex virus-2 genital tract shedding episodes

Joshua T. Schiffer, Laith Aburaddad, Karen E. Mark, Jia Zhu, Stacy Selke, David M. Koelle, Anna Wald, Lawrence Corey

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Herpes simplex virus-2 (HSV-2) shedding episodes in humans vary markedly in duration and virologic titer within an infected person over time, an observation that is unexplained. To evaluate whether host or virological factors more closely accounted for this variability, we combined measures of viral replication and CD8+ lymphocyte density in genital biopsies, with a stochastic mathematical model of HSV-2 infection. Model simulations reproduced quantities of virus and duration of shedding detected in 1,003 episodes among 386 persons. In the simulations, local CD8+ lymphocyte density in the mucosa at episode onset predicted peak HSV DNA copy number and whether genital lesions or subclinical shedding occurred. High density of CD8+ T cells in the mucosa correlated with decreased infected cell lifespan and fewer infected epithelial cells before episode clearance. If infected cell lifespan increased by 15 min because of CD8+ lymphocyte decay, then there was potential for a thousandfold increase in the number of infected cells. The model suggests that the rate of containment of infected cells by the peripheral mucosal immune system is the major driver of duration and severity of HSV-2 reactivation in the immunocompetent host.

Original languageEnglish
Pages (from-to)18973-18978
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number44
DOIs
Publication statusPublished - 2 Nov 2010
Externally publishedYes

    Fingerprint

Keywords

  • Infectious diseases
  • Mathematical modeling
  • Mucosal immunology
  • Virology

ASJC Scopus subject areas

  • General

Cite this