Insights into ZIKV-Mediated Innate Immune Responses in Human Dermal Fibroblasts and Epidermal Keratinocytes

The Journal of Investigative Dermatology
Ji-Ae KimOk Sarah Shin

Abstract

Zika virus (ZIKV) has emerged as a global pathogen causing significant public health concern. ZIKV infections in humans principally occur via mosquito bites. Thus, host skin cells are permissive to ZIKV infection and are the first line of defense against the virus. Here, we examined the role and mechanisms of antiviral skin immunity against ZIKV infection. ZIKV infection (African lineage MR766) in human dermal fibroblasts, human epidermal keratinocytes, and HaCaT keratinocytes resulted in distinct expression changes in RIG-I-like receptors, such as RIG-I and MDA5. Inhibition of RIG-I using small interfering RNA resulted in increased viral gene expression and reduced induction of IFNs and IFN-stimulated genes. Furthermore, ZIKV NS1 directly interacted with RIG-I or MDA5 and down-regulated RIG-I-like receptor-mediated antiviral signaling pathways. Asian lineage ZIKV (PRVABC59) infection also showed a distinct pattern of antiviral immunity in human skin cells, compared with other ZIKV strains. Additionally, ZIKV infections in human neural progenitor cells induced the robust activation of RIG-I-like receptor-mediated signaling, followed by highly enhanced IFN-stimulated gene expression. Our findings provide important insights into ...Continue Reading

Citations

May 2, 2019·Current Infectious Disease Reports·Xuan Qi KohPaul Anantharajah Tambyah
Sep 20, 2019·Journal of Virology·Blandine MonelOlivier Schwartz
Aug 4, 2020·PLoS Neglected Tropical Diseases·Murilo Sena AmaralSergio Verjovski-Almeida
Jul 15, 2020·Life Science Alliance·Brittany L UhlornSamuel K Campos
Mar 7, 2019·International Journal of Molecular Sciences·Jae Kyung Lee, Ok Sarah Shin
May 16, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Juan Felipe Valdés LópezSilvio Urcuqui-Inchima
May 27, 2020·Journal of Immunology Research·Patricio L AcostaLaura B Talarico
Sep 11, 2019·EBioMedicine·Alicia Martinez-LopezFelipe Diaz-Griffero
Jan 28, 2021·Nature Communications·Jianying LiuScott C Weaver
May 29, 2021·PLoS Neglected Tropical Diseases·Sergio P Alpuche-LazcanoAnne Gatignol
May 30, 2021·Virology·Utkarsh BhardwajSunit K Singh
Jul 24, 2021·Frontiers in Cellular and Infection Microbiology·Soo-Jin OhOk Sarah Shin
Sep 2, 2021·Journal of Virology·Daniel Gavino-LeopoldinoIranaia Assunção-Miranda
Nov 3, 2021·Experimental Dermatology·Mitsuhiro Denda, Shinobu Nakanishi

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