Recombination Analysis Of Enterovirus 71 In Mainland China In The Past 10 Years And LncRNA Omics Study Of Zika Virus-infected A549 Cells

Background:Surveillance of recombinant enterovirus 71(EV71)and subgenotype replacement are vital for preventing and controlling the hand,foot,and mouth disease(HFMD)outbreak.Nevertheless,the recombinant variant information and phylogeny of circulating EV71 strains in mainland China are limited.In this study,the recombinant variants of EV71 were identified systematically in mainland China from 2009 to 2018.Methods:Based on Genebank database,Virus Pathogen Database and Analysis Resource(VIPR),the complete genome sequences of 196 EV71 strains from various regions in China from 2009 to 2018 were obtained.ClustalW2 was used for sequence alignment,MEGA7 was used to construct phylogenetic dendrograms,RDP5 was used to identify natural recombinant strains within complete genome sequence alignments,the analysis was performed using SimPlot software package version 3.5.1 to further identify these recombinant strains.Results:Phylogenetic analysis indicated that except for individual strains(CQ2014-86/CQ/CHN/2014 and EV71/Xiamen/2009(B5)),almost all theEV71 strains in mainland China belonged to the subgenotype C4a.Using complete genome sequences of 196 EV71 isolates,3 intertypic recombination strains(VR1432,30-2/2015/BJ,and Guangdong-2009)and 5 intratypic recombination strains(EV71/P1034/2013,VR1432,Henan-ZMD/CHN/2012,Hubei-WH/CHN/2012,and EV71/P868/2013/China)were identified among naturally circulating EV71 isolates in mainland China during 20092018.The breakpoints of these recombinant strains are located within P1,P2,and P3 encoding regions.Notably,a "double recombinant" VR1432 resulting from recombination between EV71 subgenotype C4a and C4b strain SHZH98 and a CA8 strain Donovan was identified.Conclusion:This study,for the first time,reported these specific intertypic and intratypic recombination events that highlight the importance of genetic recombination in the emergence of new enterovirus variants.Zika virus disease is an acute,self-limited infectious disease caused by Zika virus(ZIKV).Microcephaly caused by ZIKV infection and other neurological diseases such as Guillain-Barre syndrome have become an international focus.Concerning public health events,in order to further study the interaction mechanism between ZIKV and the host,this study predicts the pathogenic mechanism of pathogens to the host from the perspective of long non-coding RNAs(lncRNA).Based on the ZIKV whole-genome sequencing data from the public database,the differences in lncRNA expression profiles of ZIKV-infected A549 cells were analyzed,so as to more systematically understand and predict the possible molecular mechanism of the interaction between the host and ZIKV.Through transcriptome sequencing technology(RNA-Seq),the differential expression profile of lncRNA in ZIKV-infected and uninfected A549 cells was screened,and the differential expression of lncRNA was analyzed by GO and KEGG.Compared with uninfected A549 cells,ZIKV-infected A549 cells showed a total of 268 different lncRNAs.Among them,121 lncRNAs were up-regulated and 147 lncRNAs were down-regulated.Among them,a total of lncRNAs were induced to express after infection.There are 36,and a total of 50 lncRNAs are completely suppressed.Differentially expressed lncRNA and its predicted neighboring genes are mainly enriched in the immune response process.After ZIKV infects A549 cells,the expression profile of lncRNA changes significantly,which lays a theoretical foundation for the in-depth study of how lncRNA participates in the interaction between ZIKV and the host,and also provides new perspectives and ideas for the molecular mechanism of ZIKV infection of the host.