RESUMEN
Zika virus (ZIKV) is a mosquito-borne flavivirus that has emerged as an important human viral pathogen, causing congenital malformation including microcephaly among infants born to mothers infected with the virus during pregnancy. Phylogenetic analysis suggested that ZIKV can be classified into African and Asian lineages. In this study, we have developed a stable plasmid-based reverse genetic system for robust production of both ZIKV prototype African-lineage MR766 and clinical Asian-lineage FSS13025 strains using a tetracycline (Tet)-controlled gene expression vector. Transcription of the full-length ZIKV RNA is under the control of the Tet-responsive Ptight promoter at the 5' end and an antigenomic ribozyme of hepatitis delta virus at the 3' end. The transcription of infectious ZIKV RNA genome was efficiently induced by doxycycline. This novel ZIKV reverse genetics system will be valuable for the study of molecular viral pathogenesis of ZIKV and the development of new vaccines against ZIKV infection.
Asunto(s)
Vectores Genéticos , Regiones Promotoras Genéticas , Genética Inversa , Tetraciclina/farmacología , Virus Zika/genética , África , Asia , Células Cultivadas , Clonación Molecular , ADN Complementario/genética , Doxiciclina/farmacología , Genoma Viral , Virus de la Hepatitis Delta/genética , Filogenia , Plásmidos , Replicación Viral , Virus Zika/patogenicidadRESUMEN
The anti-influenza activity of a series of thiobenzamide fusion inhibitors derived from 1,3,3-trimethyl-5-hydroxy-cyclohexylmethylamine is profiled. Axial disposition of the thioamide moiety is essential for potent influenza inhibitory activity.