Journal article
Yellow Fever Virus, but Not Zika Virus or Dengue Virus, Inhibits T-Cell Receptor-Mediated T-Cell Function by an RNA-Based Mechanism
The Journal of infectious diseases, Vol.216(9), pp.1164-1175
11/27/2017
DOI: 10.1093/infdis/jix462
PMCID: PMC5853456
PMID: 28968905
Abstract
The Flavivirus genus within the Flaviviridae family is comprised of many important human pathogens including yellow fever virus (YFV), dengue virus (DENV), and Zika virus (ZKV), all of which are global public health concerns. Although the related flaviviruses hepatitis C virus and human pegivirus (formerly named GBV-C) interfere with T-cell receptor (TCR) signaling by novel RNA and protein-based mechanisms, the effect of other flaviviruses on TCR signaling is unknown. Here, we studied the effect of YFV, DENV, and ZKV on TCR signaling. Both YFV and ZKV replicated in human T cells in vitro; however, only YFV inhibited TCR signaling. This effect was mediated at least in part by the YFV envelope (env) protein coding RNA. Deletion mutagenesis studies demonstrated that expression of a short, YFV env RNA motif (vsRNA) was required and sufficient to inhibit TCR signaling. Expression of this vsRNA and YFV infection of T cells reduced the expression of a Src-kinase regulatory phosphatase (PTPRE), while ZKV infection did not. YFV infection in mice resulted in impaired TCR signaling and PTPRE expression, with associated reduction in murine response to experimental ovalbumin vaccination. Together, these data suggest that viruses within the flavivirus genus inhibit TCR signaling in a species-dependent manner.
Details
- Title: Subtitle
- Yellow Fever Virus, but Not Zika Virus or Dengue Virus, Inhibits T-Cell Receptor-Mediated T-Cell Function by an RNA-Based Mechanism
- Creators
- James H McLinden - Department of Internal Medicine, University of Iowa, Iowa CityNirjal Bhattarai - Department of Internal Medicine, University of Iowa, Iowa CityJack T Stapleton - Department of Microbiology, University of Iowa, Iowa CityQing Chang - Department of Internal Medicine, University of Iowa, Iowa CityThomas M Kaufman - Department of Internal Medicine, University of Iowa, Iowa CitySuzanne L Cassel - Department of Internal Medicine, University of Iowa, Iowa CityFayyaz S Sutterwala - Department of Internal Medicine, University of Iowa, Iowa CityHillel Haim - Department of Internal Medicine, University of Iowa, Iowa CityJon C Houtman - Department of Microbiology, University of Iowa, Iowa CityJinhua Xiang - Department of Internal Medicine, University of Iowa, Iowa City
- Resource Type
- Journal article
- Publication Details
- The Journal of infectious diseases, Vol.216(9), pp.1164-1175
- DOI
- 10.1093/infdis/jix462
- PMID
- 28968905
- PMCID
- PMC5853456
- ISSN
- 0022-1899
- eISSN
- 1537-6613
- Grant note
- R56 AI126493 / NIAID NIH HHS I01 CX000821 / CSRD VA I01 BX000207 / BLRD VA
- Language
- English
- Date published
- 11/27/2017
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; Internal Medicine
- Record Identifier
- 9984083273702771
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