Pharmacological Agent GW4869 Inhibits Tick-Borne Langat Virus Replication to Affect Extracellular Vesicles Secretion.

ABSTRACT: GW4869, a cell-permeable, selective inhibitor of neutral sphingomyelinase is a pharmacological agent that blocks the production and release of extracellular vesicles (EVs). Our previous studies have shown that GW4869 inhibits flaviviral loads in tick, mosquito and mammalian cells, including murine cortical neurons. Yet the mechanism(s) of GW4869 inhibitor upon viral infections were not addressed. In the current study, we focused on how GW4869 interferes with Langat Virus (LGTV, a tick-borne flavivirus) replication in ISE6 tick cells. First, we found that GW4869 is neither cytotoxic at tested doses of 50, 100, and 150 µM in tick cells, nor does it directly bind to the free LGTV present in cell culture supernatants. When tick cells were treated with GW4869, followed by infection with viral s

SUBMITTER: Bayzid M 

PROVIDER: S-EPMC12298192 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature