@techreport{fdi:010089453, title = {{R}ole of cholesterol, {SAMHD}1 protein and {A}edes aegypti saliva on {C}hikungunya virus infection in human skin fibroblasts}, author = {{W}ichit, {S}.}, editor = {}, language = {{ENG}}, abstract = {{C}hikungunya virus ({CHIKV}) is a re-emerging mosquito-borne alphavirus that has been spread worldwide. {T}he dissemination of this virus is a threat to human health since there is no approved vaccine or appropriate antiviral agents to control viral infection. {T}he global expansion of the virus is preceded by biting of infected {A}edes mosquitos, which injects saliva containing the virus into the skin of the human host. {S}earching for effective antiviral compounds and understanding of the molecular mechanisms involved in host-virus or vector-virus-host interactions are crucial for controlling viral spread.{U}sing different molecular and cellular strategies, we demonstrated that the {FDA} approved drug, imipramine, which has the capability to disturb intracellular cholesterol transport inhibits {CHIKV} replication in human skin fibroblasts. {I}mipramine was found to affect both the fusion and replication steps of the viral life cycle. {M}oreover, it also strongly inhibited the replication of several {F}laviviridae family members, including {Z}ika, {W}est {N}ile and {D}engue virus. {W}e have also determined the global proteomic profile of {C}hikungunya and {Z}ika virus infected human skin fibroblasts, and found that several interferon-stimulated proteins and antiviral response proteins are significantly up-regulated in the infected cells. {M}ore importantly, our results also provided for the first time a role of {SAMHD}1 in arbovirus infection of human skin fibroblasts. {F}inally, we demonstrated that {A}edes aegypti saliva enhances {CHIKV} replication in human skin fibroblasts. {T}o our knowledge, this is the first report showing the importance of {A}edes aegypti saliva on promoting {CHIKV} infection via down regulation of the genes involving type {I} {IFN} secretion in the infected human cutaneous cells.}, keywords = {}, address = {{M}ontpellier}, publisher = {{U}niv. de {M}ontpellier ; {IRD} ; {INSERM}}, series = {}, pages = {158 multigr.}, year = {2017}, URL = {https://www.documentation.ird.fr/hor/fdi:010089453}, }