Baculovirus Actin Rearrangement-Inducing Factor 1 Can Remodel the Mammalian Actin Cytoskeleton

The actin rearrangement-inducing factor 1 (Arif-1) of Autographa californicamultiple nucleopolyhedrovirus (AcMNPV) is an early viral protein that manipulates theactin cytoskeleton of host insect cells. Arif-1 is conserved among alphabaculoviruses andis responsible for the accumulation of F-actin at the plasma membrane during the earlyphase of infection. However, the molecular mechanism underlying Arif-1-induced corticalactin accumulation is still open. Recent studies have demonstrated the formation ofinvadosome-like structures induced by Arif-1, suggesting a function in systemic virusspread. Here, we addressed whether Arif-1 is able to manipulate the actin cytoskeletonof mammalian cells comparably to insect cells. Strikingly, transient overexpression ofArif-1 in B16-F1 mouse melanoma cells revealed pronounced F-actin remodeling. Actinassembly was increased, and intense membrane ruffling occurred at the expense of substrate-associated lamellipodia. Deletion mutagenesis studies of Arif-1 confirmed that theC-terminal cytoplasmic region was not sufficient to induce F-actin remodeling, supportingthat the transmembrane region for Arif-1 function is also required in mammaliancells. The similarities between Arif-1-induced actin remodeling in insect and mammaliancells indicate that Arif-1 function relies on conserved cellular interaction partners and signaltransduction pathways, thus providing an experimental tool to elucidate the underlyingmechanism.