Effect of fatty acids on arenavirus replication: inhibition of virus production by lauric acid

To study the functional involvement of cellular membrane properties on aren avirus infection, saturated fatty acids of variable chain length (C10-C18) were evaluated for their inhibitory activity against the multiplication of Junin virus (JUNV). The most active inhibitor was lauric acid (C12), which reduced virus yields of several attenuated and pathogenic strains of JUNV i n a dose dependent manner, without affecting cell viability. Fatty acids wi th shorter or longer chain length had a reduced or negligible anti-JUNV act ivity. Lauric acid did not inactivate virion infectivity neither interacted with the cell to induce a state refractory to virus infection. From mechan istic studies, it can be concluded that lauric acid inhibited a late matura tion stage in the replicative cycle of JUNV. Viral protein synthesis was no t affected by the compound, but the expression of glycoproteins in the plas ma membrane was diminished. A direct correlation between the inhibition of JUNV production and the stimulation of triacylglycerol cell content was dem onstrated, and both lauric-acid induced effects were dependent on the conti nued presence of the fatty acid. Thus, the decreased insertion of viral gly coproteins into the plasma membrane, apparently due to the increased incorp oration of triacylglycerols, seems to cause an inhibition of JUNV maturatio n and release.