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.
Drinking arsenic (As)-laden water for a long time affects a population's health and leads to chronic hydroarsenicism, which is associated with an increased incidence of different types of cancer. To determine the potential genotoxic risk associated with different degrees of environmental exposure to inorganic As by way of drinking water, micronuclei (MN) frequency in exfoliated buccal cells was evaluated in Argentina among rural populations of Santiago del Estero and urban populations of Buenos Aires. The exposed group in Santiago del Estero (La Firmeza and Santos Lugares localities) showed a significant increase in MN frequency in epithelial cells compared with controls (Monte Quemado and Urutau localities) (p = 0.0005). With regard to the Buenos Aires groups, Navarro individuals (the exposed group) exhibited a significant difference compared with controls (Ciudad Autónoma de Buenos Aires) (p = 0.0002). Comparison of MN frequencies between Santiago del Estero and Buenos Aires individuals showed that genotoxic effects of As in drinking water exhibit variation between rural and urban groups, probably due to individual susceptibility being an important incidence factor. The results clearly show that MN assay in buccal mucosa cells is an ideal methodology with which to measure potential genetic risk related to environmental As exposure in humans.
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