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 ZIKV tropism and subsequent antiviral signaling pathways that regulate ZIKV replication in human dermal fibroblasts and human epidermal keratinocytes.
| Original language | English |
|---|---|
| Journal | Journal of Investigative Dermatology |
| DOIs | |
| Publication status | Accepted/In press - 2018 Jan 1 |
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ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Dermatology
- Cell Biology
Cite this
Insights into ZIKV-Mediated Innate Immune Responses in Human Dermal Fibroblasts and Epidermal Keratinocytes. / Kim, Ji Ae; Seong, Rak Kyun; Son, Sang Wook; Shin, Ok.
In: Journal of Investigative Dermatology, 01.01.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Insights into ZIKV-Mediated Innate Immune Responses in Human Dermal Fibroblasts and Epidermal Keratinocytes
AU - Kim, Ji Ae
AU - Seong, Rak Kyun
AU - Son, Sang Wook
AU - Shin, Ok
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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 ZIKV tropism and subsequent antiviral signaling pathways that regulate ZIKV replication in human dermal fibroblasts and human epidermal keratinocytes.
AB - 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 ZIKV tropism and subsequent antiviral signaling pathways that regulate ZIKV replication in human dermal fibroblasts and human epidermal keratinocytes.
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UR - http://www.scopus.com/inward/citedby.url?scp=85056809368&partnerID=8YFLogxK
U2 - 10.1016/j.jid.2018.07.038
DO - 10.1016/j.jid.2018.07.038
M3 - Article
C2 - 30218650
AN - SCOPUS:85056809368
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
ER -