This observation suggests that the translation of cell line-based findings of ZIKV biology to more complex physiological systems should be done with precaution

This observation suggests that the translation of cell line-based findings of ZIKV biology to more complex physiological systems should be done with precaution. data suggest that a large collection of computer virus isolates needs to be investigated before conclusions on lineage differences can be made. Introduction Zika computer virus (ZIKV) is an emerging mosquito-borne of the family causing congenital ZIKV syndrome, including microcephaly, and severe neurological complications in adults1,2. Originally, the computer virus was isolated from a rhesus macaque in 1947 in the Zika Forest of Uganda3. ZIKV is mainly transmitted by mosquitoes of the genus such as C6/36 cells. Next, we tried to extrapolate our findings by identifying potential differences between African and Asian lineages in a relevant cell type involved in flavivirus pathogenesis. Indeed, as a more physiological cellular model of ZIKV contamination, we analyzed contamination parameters and IFN pathway induction at the level of IFNs and ISGs in human MoDCs. The levels of sfRNA produced upon contamination of MoDCs by the different ZIKV strains tested have also been evaluated. Results Strain-specific contamination profiles in Vero and C6/36 cells We used Vero and C6/36 cells as standard cell types for flavivirus work to evaluate the infection profiles of ZIKV strains of the African and the Asian lineages. The prototypic strains MR766 (from here referred as U-1947), originally isolated from a sentinel monkey, and MP1751 (referred as U-1962), isolated from a pool of mosquitoes (settings. First, we observed strain-related susceptibility of the vertebrate Vero cell collection towards African and Asian ZIKV strains and compared it to the invertebrate C6/36 cell collection, both commonly used for ZIKV propagation. Second, we analyzed the infection profiles of human MoDCs infected with ZIKV and measured IFNs Epothilone A response at the level of IFN-, IFN-s and ISGs and didnt noticed lineage-dependent differences. Finally, to investigate mechanisms of ZIKV-induced IFN pathway inhibition, we measured the levels of ZIKV sfRNA and observed comparable levels between strains. In comparison to MoDCs, we measured higher contamination rates in Vero and C6/36 Rabbit Polyclonal to RBM34 cells Epothilone A challenged with several ZIKV strains but comparable live computer virus release. Indeed, unlike with infected Vero and C6/36 cells, the percentage of infected MoDCs did not follow over time ZIKV replication assayed by live computer virus titration and RT-PCR. This observation suggests that the translation of cell line-based findings of ZIKV biology to more complex physiological systems should be done with precaution. Susceptibility of human MoDCs towards U-1947 strain and currently circulating PR-2015 strain has been previously observed by Bowen showing no significant cellular death of Epothilone A infected human MoDCs with four different ZIKV strains at 48?h p.i. with higher MOIs than used in our study34. The available studies investigating the cytopathic effect of African and Asian ZIKV strains are puzzling and seem to be dependent on the cellular target evaluated. Indeed, studies investigating virulence of ZIKV in human neural cells show a lower cytopathic effect of Asian compared to African lineage strains36,37. In addition, human endometrial stromal cells showed higher cell-death response after contamination with U-1947 compared to a contemporary Asian strain38. However, in an contamination model of vascular endothelial cells with a circulating PR-2015 isolate and U-1947 strain, the authors observed that this circulating Puerto Rican isolate is usually inducing stronger cell death and faster viral RNA replication rates compared to an African isolate39. In a recent study, Dowall in 1962 and has been passaged up to four occasions between 1962 and 1972 by an unknown method followed by one passage in Vero cells in 2011 (PHE). The low passage ZIKV clinical isolates (<5 passages) of the Asian lineage were obtained from viremic patients in French Polynesia in 2013 (FP-2013; PF13/25013-18; GenBank "type":"entrez-nucleotide","attrs":"text":"KX369547","term_id":"1040461413","term_text":"KX369547"KX369547), and in Puerto Rico in 2015 (PR-2015; PRVABC59; GenBank "type":"entrez-nucleotide","attrs":"text":"KX377337","term_id":"1036637434","term_text":"KX377337"KX377337) and in Guadeloupe (G-2016; PHE_Semen_Guadeloupe; GenBank "type":"entrez-nucleotide","attrs":"text":"KX673530","term_id":"1050405299","term_text":"KX673530"KX673530) in 2016.