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.

From the in vivo studies in NHPs, it was expected for virus to release infectious particles from primarily the apical side, since viral particles were not detected in any tissues after intragastric infection with LCMV [23] . However, when exposed on the apical side of epithelial cells, LCMV and MOPV primarily released on the apical side of the cells, but release basolaterally was observed. This observation indicates that the epithelial barrier is not the sole determinant of viral dissemination. Interesting to note as well, was that patterns of replication were similar regardless of the in vivo pathogenicity of the LCMV strains. Therefore, the infectious capacity of these viruses in vitro, in regards to Caco-2 cells, does not correlate with pathogenic properties for LCMV. Therefore, further investigation as to the driving forces of pathogenic differences needs to be investigated. However, in contrast to LCMV, the ML-29 expressing LASV GP1, predominantly released viral particles apically regardless of the route of entry. Furthermore, these results demonstrate that MOPV entry-release pattern in polarized Caco-2 cells resembled those in cells infected with LCMV, and was clearly different from ML29-driving entry-release. Due to ML-29 replication patterns being different than that of MOPV replication, these patterns of entry and release are not due to MOPV replication machinery, and may be attributed to the gene products of the S segment of LASV, namely the glycoproteins and nucleoprotein. This poor replication and egress to the basolateral sides of the cells is an interesting observation. While ML-29 is not WT-LASV, using WT-LASV in similar studies could lead to an explanation as to why almost half of the population of endemic regions are seropositive for LASV, but never demonstrated clinical signs of disseminated illness. In addition, the data presented here indicates that the capacity to infect via the apical surface of intestinal epithelial cells is not a primary determinant of arenavirus pathogenesis.