Zika virus triggers autophagy to exploit host lipid metabolism and drive viral replication

• DOI: 10.1186/s12964-022-01026-8
• Publication Date: 2023-05-19T13:02:23Z
• Authors: Gloria Stoyanova; Sidra Jabeen; Joselyn Landazuri...; Sounak Ghosh Roy; Richard A. Lockshin; Zahra Zakeri
• Keywords: Zika Virus; Lipid droplet; Flavivirus

Abstract Background Zika virus (ZIKV), an arbovirus of global concern, has been associated with neurological complications including microcephaly in newborns and Guillain–Barré syndrome adults. Like other flaviviruses, ZIKV depends on cholesterol to facilitate its replication; thus, proposed as a therapeutic target treat the infection using FDA-approved statins. Cholesterol is stored intracellular lipid droplets (LD) form esters can be regulated by autophagy. We hypothesize that hijacks autophagy machinery early step increase formation LD viral replication, interference this pathway will limit reproduction virus. Methods pretreated MDCK cells atorvastatin or inhibitors prior ZIKV. measured expression qPCR for NS1 RNA immunofluorescence E protein. Results Autophagy increases virus-infected 6 h post (hpi). In presence atorvastatin, are decreased, reduced, targeting key steps resulting suppression replication suppressed. Other both early- late-acting decrease number replication. Bafilomycin renders inaccessible also confirm previous reports bystander effect, which neighboring uninfected have higher counts compared infected cells. Conclusions conclude lead lower availability LD, decreasing bafilomycin A1 inhibits blocking esterification LD. Graphical