@article{fdi:010065255,
  title = {{B}iology of {Z}ika virus infection in human skin cells},
  author = {{H}amel, {R}odolphe and {D}ejarnac, {O}. and {W}ichit, {S}. and {E}kchariyawat, {P}. and {N}eyret, {A}. and {L}uplertlop, {N}. and {P}erera-{L}ecoin, {M}. and {S}urasombatpattana, {P}. and {T}alignani, {L}. and {T}homas, {F}. and {C}ao-{L}ormeau, {V}. and {C}houmet, {V}. and {B}riant, {L}. and {D}espr{\`e}s, {P}. and {A}mara, {A}. and {Y}ssel, {H}. and {M}iss{\'e}, {D}oroth{\'e}e},
  editor = {},
  language = {{ENG}},
  abstract = {{Z}ika virus ({ZIKV}) is an emerging arbovirus of the {F}laviviridae family, which includes dengue, {W}est {N}ile, yellow fever, and {J}apanese encephalitis viruses, that causes a mosquito-borne disease transmitted by the {A}edes genus, with recent outbreaks in the {S}outh {P}acific. {H}ere we examine the importance of human skin in the entry of {ZIKV} and its contribution to the induction of antiviral immune responses. {W}e show that human dermal fibroblasts, epidermal keratinocytes, and immature dendritic cells are permissive to the most recent {ZIKV} isolate, responsible for the epidemic in {F}rench {P}olynesia. {S}everal entry and/or adhesion factors, including {DC}-{SIGN}, {AXL}, {T}yro3, and, to a lesser extent, {TIM}-1, permitted {ZIKV} entry, with a major role for the {TAM} receptor {AXL}. {T}he {ZIKV} permissiveness of human skin fibroblasts was confirmed by the use of a neutralizing antibody and specific {RNA} silencing. {ZIKV} induced the transcription of {T}oll-like receptor 3 ({TLR}3), {RIG}-{I}, and {MDA}5, as well as several interferon-stimulated genes, including {OAS}2, {ISG}15, and {MX}1, characterized by strongly enhanced beta interferon gene expression. {ZIKV} was found to be sensitive to the antiviral effects of both type {I} and type {II} interferons. {F}inally, infection of skin fibroblasts resulted in the formation of autophagosomes, whose presence was associated with enhanced viral replication, as shown by the use of {T}orin 1, a chemical inducer of autophagy, and the specific autophagy inhibitor 3-methyladenine. {T}he results presented herein permit us to gain further insight into the biology of {ZIKV} and to devise strategies aiming to interfere with the pathology caused by this emerging flavivirus. {IMPORTANCE} {Z}ika virus ({ZIKV}) is an arbovirus belonging to the {F}laviviridae family. {V}ector-mediated transmission of {ZIKV} is initiated when a blood-feeding female {A}edes mosquito injects the virus into the skin of its mammalian host, followed by infection of permissive cells via specific receptors. {I}ndeed, skin immune cells, including dermal fibroblasts, epidermal keratinocytes, and immature dendritic cells, were all found to be permissive to {ZIKV} infection. {T}he results also show a major role for the phosphatidylserine receptor {AXL} as a {ZIKV} entry receptor and for cellular autophagy in enhancing {ZIKV} replication in permissive cells. {ZIKV} replication leads to activation of an antiviral innate immune response and the production of type {I} interferons in infected cells. {T}aken together, these results provide the first general insights into the interaction between {ZIKV} and its mammalian host.},
  keywords = {},
  booktitle = {},
  journal = {{J}ournal of {V}irology},
  volume = {89},
  numero = {17},
  pages = {8880--8896},
  ISSN = {0022-538{X}},
  year = {2015},
  DOI = {10.1128/jvi.00354-15},
  URL = {https://www.documentation.ird.fr/hor/fdi:010065255},
}