Filovirus Tropism: Cellular Molecules for Viral Entry

Takada, Ayato

Both MARV and EBOV GPs contain both N-and O-linked carbohydrate chains with different terminal sialylation patterns that seem to depend on the virus strains and cell lines used for their propagation. The MLR contains a number of potential N-and Olinked glycosylation sites as mentioned above. Though the MLR is found in all known filovirus GPs, its highly variable amino acid sequences and sugar chain structure suggest different GP properties among filovirus species. Interestingly, it is well documented that deletion of the MLR does not affect the fundamental function of GP in viral entry into cells in vitro, as indicated by the observation that pseudotyped viruses bearing GP lacking the MLR infect primate epithelial cells (e.g.,Vero E6 cells) similarly or rather more efficiently than viruses with wild-type GP (Simmons et al., 2002; Takada et al., 2004; Matsuno et al., 2010a) . According to the crystal structure of ZEBOV GP in its trimeric, prefusion conformation, the MLR may restrict access of the putative RBR to virus receptors (Lee et al., 2008) . Thus, pseudotyped viruses bearing MLR-deletion mutant GP have often been used for approaches to identify filovirus-specific receptors (Shimojima et al., 2006; Kondratowicz et al., 2011) . However, the MLR plays an important role in filovirus entry into preferred target cells such as endothelial cells, hepatocytes, and antigen-presenting cells, whose infection is likely involved in tropism and pathogenesis of filoviruses, as described below.