West Nile Virus Capsid Degradation of Claudin Proteins Disrupts Epithelial Barrier Function

Abstract

During acute infection, West Nile virus (WNV) has been reported to infect a variety of cell types in various tissues of both experimentally and naturally infected hosts. Virus infects epithelial cells in the skin, kidney, intestine, and testes, although the importance of these findings is unclear. In the current study, we have observed that WNV infection of kidney tubules in mice coincides with the loss of expression of several members of the claudin family. Proteins of this family are often involved in epithelial barrier formation and function. WNV infection of epithelial cells in culture resulted in a decrease in the transepithelial electrical resistance, an increase in the efflux of mannitol across the monolayer, and a loss of intracellular levels of claudin-1 to -4. WNV capsid alone was sufficient for the degradation event, which was mediated through lysosomal proteases. Since epithelial cells are frequent sites of WNV infection, these observations imply a potential mechanism for virus dissemination and extraneural pathogenesis.

Uncoupling cis -Acting RNA Elements from Coding Sequences Revealed a Requirement of the N-Terminal Region of Dengue Virus Capsid Protein in Virus Particle Formation

“…Although DENV showed a requirement of basic residues at the N terminus of C for efficient encapsidation in mosquito cells, the remarkable reduction in viral particle formation in mammalian cells suggests a possible role of the N terminus of C in a host-virus interaction. It has been reported previously that the C protein of flaviviruses is involved in the induction of apoptosis and the breakdown of cellular tight junctions (26,37,44). A growing number of host proteins that interact with flavivirus C proteins have been reported (4,5,18,28).…”

Induction of the Cellular MicroRNA, Hs_154, by West Nile Virus Contributes to Virus-Mediated Apoptosis through Repression of Antiapoptotic Factors

“…HeLa, Huh7, and Huh7.5 cells were grown in Dulbecco modified Eagle medium supplemented with 10% FBS, 2 mM L-glutamine, 100 U of penicillin G sodium/ml, and 100 g of streptomycin sulfate/ml. WNV 385-99 (55) and dengue virus 2 (New Guinea C strain; American Type Culture Collection) were passaged twice on C6/36 cells and purified by centrifugation as previously described (31). Virus titers were determined using a by focus formation assay.…”

Infección por virus del Zika en el embarazo, impacto fetal y neonatal

“…Sin embargo, no es completamente conocido. Una de las rutas, es la disrupción de las uniones intercelulares herméticas (UIH), a través de la alteración de la claudina 26,27 , un componente esencial de estas UIH, promoviendo el transporte de los FV que se encuentran libres o dentro de los linfocitos o neutrófilos (fenómeno conocido como caballo de Troya) a través de la barrera hemato-encefálica (BHE), los plexos coroides y la glía (astrocitos y microglia) 28,29 . La otra ruta de neuroinvasión de los FV es el resultado del transporte axonal neuronal en dirección antero y retrógrada desde la periferia (durante la viremia) a través de la médula espinal o el bulbo olfatorio, dando lugar a la apoptosis de la neurona anterior del cuerno espinal, siendo compatible con los datos de parálisis flácida aguda 30,31 .…”