Mammarenaviral Infection Is Dependent on Directional Exposure to and Release from Polarized Intestinal Epithelia

Warner, Nikole L.; Jokinen, Jenny D.; Beier, Juliane I.; Sokoloski, Kevin J.; Lukashevich, Igor S.

To conclude, our data above demonstrates that the polarized Caco-2 system is a viable model to investigate the interaction of intestinal epithelial cells during viral infection with OW mammarenaviruses. These polarized epithelia closely mimic intestinal epithelial of human hosts and allow further investigation of mammarenaviral infection at the epithelial barrier. These data with LCMV show that intestinal epithelial cells may not be the sole determinant of viral pathogenesis and dissemination. Furthermore, differences between prototypic arenavirus LCMV and the surrogate model of LASV interaction, ML-29, were observed in both attachment efficiency and viral entry and egress from polarized intestinal epithelia. These results may potentially explain the high penetrance without disease observed for LASV. In addition, ML-29's diminished binding efficiency to the basolateral side of polarized Caco-2 cells supports the expanding complexity of arenavirus receptor interactions. Collectively, these studies show that arenaviral infection of polarized cells is not only viral specific, but ultimately may be tissue and host-specific as well; and that arenavirus infection and pathogenesis may be dependent on asymmetric distribution of viral and cellular factors required for virus entry and budding.