p38MAPK plays a critical role in induction of a pro-inflammatory phenotype of retinal Müller cells following Zika virus infection

Shuang Zhu, Huanle Luo, Hua Liu, Yonju Ha, Elizabeth R. Mays, Ryan E. Lawrence, Evandro Winkelmann, Alan D. Barrett, Sylvia B. Smith, Min Wang, Tian Wang, Wenbo Zhang

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Zika virus (ZIKV) infection has been associated with ocular abnormalities such as chorioretinal atrophy, optic nerve abnormalities, posterior uveitis and idiopathic maculopathy. Yet our knowledge about ZIKV infection in retinal cells and its potential contribution to retinal pathology is still very limited. Here we found that primary Müller cells, the principal glial cells in the retina, expressed a high level of ZIKV entry cofactor AXL gene and were highly permissive to ZIKV infection. In addition, ZIKV-infected Müller cells exhibited a pro-inflammatory phenotype and produced many inflammatory and growth factors. While a number of inflammatory signaling pathways such as ERK, p38MAPK, NF-κB, JAK/STAT3 and endoplasmic reticulum stress were activated after ZIKV infection, inhibition of p38MAPK after ZIKV infection most effectively blocked ZIKV-induced inflammatory and growth molecules. In comparison to ZIKV, Dengue virus (DENV), another Flavivirus infected Müller cells more efficiently but induced much lower pro-inflammatory responses. These data suggest that Müller cells play an important role in ZIKV-induced ocular pathology by induction of inflammatory and growth factors in which the p38MAPK pathway has a central role. Blocking p38MAPK may provide a novel approach to control ZIKV-induced ocular inflammation.

Original languageEnglish (US)
Pages (from-to)70-81
Number of pages12
JournalAntiviral research
Volume145
DOIs
StatePublished - Sep 2017

Keywords

  • Inflammation
  • Müller cells
  • Ocular abnormalities
  • Zika virus
  • p38MAPK

ASJC Scopus subject areas

  • Pharmacology
  • Virology

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