Date of Award

Summer 8-1-2021

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

School

Biological, Environmental, and Earth Sciences

Committee Chair

Dr. Fengwei Bai

Committee Chair School

Biological, Environmental, and Earth Sciences

Committee Member 2

Dr. Janet R Donaldson

Committee Member 2 School

Biological, Environmental, and Earth Sciences

Committee Member 3

Dr. Mohamed O Elasri

Committee Member 3 School

Biological, Environmental, and Earth Sciences

Committee Member 4

Dr. Yan-Lin Guo

Committee Member 4 School

Biological, Environmental, and Earth Sciences

Committee Member 5

Dr. Shahid Karim

Committee Member 5 School

Biological, Environmental, and Earth Sciences

Abstract

Interferons (IFNs) are the key components of innate immunity and are crucial for host defense against viral infections. Here, we report a novel role of interleukin-17A (IL-17A) in inhibiting IFN-α2 expression, thus promoting chikungunya virus (CHIKV) infection. CHIKV infected IL-17A deficient (Il17a-/-) mice expressed a higher level of IFN-α2 and developed diminished viremia and milder footpad swelling in comparison to wild-type (WT) control mice, this was also recapitulated in IL-17A receptor-deficient (Il17ra-/-) mice. Interestingly, IL-17A selectively blocked IFN-α2 production during CHIKV, but not West Nile virus (WNV) or Zika virus (ZIKV), infections. Recombinant IL-17A treatment inhibited CHIKV-induced IFN-α2 expression and enhanced CHIKV replication in both human and mouse cells. We further found that IL-17A inhibited IFN-α2 production by modulating the expression of Interferon Regulatory Factor-5 (IRF-5), IRF-7, IFN-stimulated gene 49 (ISG-49), and Mx1 expression during CHIKV infection. Neutralization of IL-17A in vitro leads to the increase of the expression of these antiviral molecules and the decrease of CHIKV replication. Collectively, these results suggest a novel function of IL-17A in inhibiting IFN-α2-mediated antiviral responses during CHIKV infection, which may have broad implications in viral infections and other inflammatory diseases.

Available for download on Monday, December 20, 2021

Included in

Virology Commons

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