@article{fdi:010093504, title = {{IFITM}s exhibit antiviral activity against {C}hikungunya and {Z}ika virus infection via the alteration of {TLR}s and {RLR}s signaling pathways}, author = {{G}umpangseth, {N}. and {V}illarroel, {P}. {M}. {S}. and {D}iack, {A}. and {S}onghong, {T}. and {Y}ainoy, {S}. and {H}amel, {R}odolphe and {K}hanom, {W}. and {K}oomhin, {P}. and {P}unsawad, {C}. and {S}rikiatkhachorn, {A}. and {M}iss{\'e}, {D}oroth{\'e}e and {S}aetear, {P}. and {W}ichit, {S}.}, editor = {}, language = {{ENG}}, abstract = {{C}hikungunya virus ({CHIKV}) poses a significant challenge as there are currently no targeted antiviral drugs or vaccines to combat this infection. {H}ere, we demonstrate that interferon-induced transmembrane proteins ({IFITM}s), including {IFITM}1, {IFITM}2, and {IFITM}3, which are interferon-stimulated genes ({ISG}s), inhibit {CHIKV} infection in human skin fibroblasts. {O}verexpression of {IFITM}s in cells restricts viral infection, whereas knockdown of {IFITM}s enhances viral infection. {IFITM}s overexpression causes a substantial upregulation of antiviral genes, namely {TLR}3, {TLR}7, {TLR}8, and {TLR}9, and their downstream signaling molecules such as {TRADD}, {IRAK}1, {TRAF}6, and {MAP}3{K}7, involved in {TLR}s signaling pathways. {F}urthermore, the {DHX}58 gene encoding the {LGP}2 protein, a negative regulator of {RIG}-{I} in {RLR}s signaling pathways, was downregulated in the overexpressed cells. {T}ranscription factors including interferon regulatory factors ({IRF}) 3/5/7, which are downstream signaling components of both {TLR} and {RLR} signaling pathways, were also upregulated, resulting in enhanced {IFN}s signaling. {IFITM}s not only inhibits the early and late stages of viral infection but can also alter the antiviral innate-immune response to restrict {CHIKV} infection in human skin fibroblasts. {A}dditionally, {IFITM}s exhibit their antiviral activity against {Z}ika virus ({ZIKV}). {A}ltogether, these results show the broad-spectrum antiviral property of {IFITM}s against arboviruses in foreskin cells.}, keywords = {{C}hikungunya virus ; {Z}ika virus ; {IFITM}s ; {A}rbovirus ; {TLR}s and {RLR}s ; signaling pathways}, booktitle = {}, journal = {{S}cientific {R}eports - {N}ature}, volume = {15}, numero = {1}, pages = {15769 [13 p.]}, ISSN = {2045-2322}, year = {2025}, DOI = {10.1038/s41598-025-00663-6}, URL = {https://www.documentation.ird.fr/hor/fdi:010093504}, }