Study of the role of the membrane protein caveolin-1 on Zika virus replication inside THP-1 cells.

Abstract

Zika virus (ZIKV) is an arthropod-borne Flavivirus that affect millions of people worldwide. Its genome is composed of a single-stranded positive RNA that encodes 10 known proteins. It can be transmitted by mosquitos of the Aedes genus, as well as by sexual intercourse and blood transfusion. Although the symptoms of acute ZIKV infection are usually mild and self-limited, it causes microcephaly in fetuses of pregnant women, and Guillian–Barré syndrome in adults. Since no treatment or vaccine has been developed until today, further studies are needed to characterize the interaction between ZIKV proteins and host cells. Recent studies have shown that lipid rafts are known to be preferred sites for interaction between viruses and host cells, which may trigger molecular signaling to favor virus multiplication. Caveolae lipid rafts are a subset of membrane rafts, which molecular marker is caveolin-1 protein, since is the responsible for caveolae formation. They are cellular domains that concentrate plasma membrane proteins and lipids involved in the regulation of cell function, which serve as an organizing center for biological phenomena and cellular signaling. Caveolae lipid rafts involvement in ZIKV processing, replication, and assembly remains poorly characterized. Here, we hypothesized a potential implication of caveolin-1 protein in the replication process for ZIKV inside the cell. This was evaluated by measuring the effect of ZIKV infection on cav-1 expression. Then, it was also studied the effect of lipid raft removal with β-methyl cyclodextrin (β-MCD) and both silencing and overexpression of cav-1, on viral multiplication, using qrt-PCR to detect ZIKV mRNA load on the cell. A decreased of cav-1 expression was observed after infection, suggesting a possible virus modulating role. Furthermore, when cellular cholesterol was depleted by β-MCD treatment after ZIKV entrance, lipid rafts were disrupted and virus genome copies were reduced inside the cell. Additionally, neither cav-1 silencing nor overexpression showed any consistent effect on ZIKV replication. These data suggest an important role of caveolar cholesterol-rich lipid raft microdomains in ZIKV replication, nevertheless further studies need to be made to confirm a specific effect of cav-1 over ZIKV multiplication.