West Nile Virus Infection Causes Endocytosis of a Specific Subset of Tight Junction Membrane Proteins

Abstract

West Nile virus (WNV) is a blood-borne pathogen that causes systemic infections and serious neurological disease in human and animals. The most common route of infection is mosquito bites and therefore, the virus must cross a number of polarized cell layers to gain access to organ tissue and the central nervous system. Resistance to trans-cellular movement of macromolecules between epithelial and endothelial cells is mediated by tight junction complexes. While a number of recent studies have documented that WNV infection negatively impacts the barrier function of tight junctions, the intracellular mechanism by which this occurs is poorly understood. In the present study, we report that endocytosis of a subset of tight junction membrane proteins including claudin-1 and JAM-1 occurs in WNV infected epithelial and endothelial cells. This process, which ultimately results in lysosomal degradation of the proteins, is dependent on the GTPase dynamin and microtubule-based transport. Finally, infection of polarized cells with the related flavivirus, Dengue virus-2, did not result in significant loss of tight junction membrane proteins. These results suggest that neurotropic flaviviruses such as WNV modulate the host cell environment differently than hemorrhagic flaviviruses and thus may have implications for understanding the molecular basis for neuroinvasion.

Structural Studies of Chikungunya Virus-Like Particles Complexed with Human Antibodies: Neutralization and Cell-to-Cell Transmission

“…The escape mutation R82G in domain A of E2 was generated under the neutralizing pressure of MAb 5F10 and was previously shown to promote the transmission of CHIKV isolates by direct cell-to-cell transfer of the virus (16). Although cell-to-cell transmission of viruses has been observed for many lipid-enveloped viruses (36)(37)(38), little is known about the exact mechanism. Nevertheless, it is known that cell-to-cell transmission is often accompanied by the increased concentration of molecules that can act as receptors (for instance, decay-accelerating factor) (39) for the free virus near cell junctions (39).…”

Viruses in human central nervous system — invasion, transmission, and latency: a literature review

“…Проникновение в ЦНС гематогенным путем сопровождается активацией продукции матриксных металлопротеиназ, учас твующих в протеолити-ческом расщеплении базальной мембраны микро-васкулярного эндотелия [36]. Вирусы HIV и HTLV-1 также разрушают ГЭБ посредством воздействия на плотные соединения микроваскулярного эндотелия [29,37].…”

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 .…”