To study the functional involvement of cellular membrane properties on
arenavirus 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 in a dose dependent manner, without affecting cell viability.
Fatty acids with shorter or longer chain length had a reduced or negligible anti-JUNV activity.
Lauric acid did not inactivate virion infectivity neither interacted with the cell to induce a state refractory to
virus infection. From mechanistic studies, it can be concluded that
lauric acid inhibited a late maturation stage in the replicative cycle of JUNV.
Viral protein synthesis was not affected by the compound, but the expression of
glycoproteins in the plasma membrane was diminished. A direct correlation between the inhibition of JUNV production and the stimulation of
triacylglycerol cell content was demonstrated, and both
lauric-acid induced effects were dependent on the continued presence of the
fatty acid. Thus, the decreased insertion of viral
glycoproteins into the plasma membrane, apparently due to the increased incorporation of
triacylglycerols, seems to cause an inhibition of JUNV maturation and release.