CD4+ and CD8+ T-cell immunity to Dengue - lessons for the study of Zika virus

Immunology. 2017 Feb;150(2):146-154. doi: 10.1111/imm.12681. Epub 2016 Nov 27.

Abstract

Dengue virus (DENV) and Zika virus (ZIKV) are rapidly emerging mosquito-borne flaviviruses that represent a public health concern. Understanding host protective immunity to these viruses is critical for the design of optimal vaccines. Over a decade of research has highlighted a significant contribution of the T-cell response to both protection and/or disease enhancement during DENV infection, the latter being mainly associated with sub-optimal cross-reactive T-cell responses during secondary infections. Phase IIb/III clinical trials of the first licensed tetravalent dengue vaccine highlight increased vaccine efficacy in dengue-immune as opposed to dengue-naive vaccinees, suggesting a possible immunoprotective role of pre-existing DENV-specific T cells that are boosted upon vaccination. No vaccine is available for ZIKV and little is known about the T-cell response to this virus. ZIKV and DENV are closely related viruses with a sequence identity ranging from 44% and 56% for the structural proteins capsid and envelope to 68% for the more conserved non-structural proteins NS3/NS5, which represent the main targets of the CD4+ and CD8+ T-cell response to DENV, respectively. In this review we discuss our current knowledge of T-cell immunity to DENV and what it can teach us for the study of ZIKV. The extent of T-cell cross-reactivity towards ZIKV of pre-existing DENV-specific memory T cells and its potential impact on protective immunity and/or immunopathology will also be discussed.

Keywords: T cells; cell trafficking; human; memory; virus.

Publication types

  • Review

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Culicidae
  • Dengue / immunology*
  • Dengue Virus / immunology*
  • Humans
  • Immunity, Cellular
  • Zika Virus / immunology*
  • Zika Virus Infection / immunology*