The rotavirus A (RV-A) virions, known as triple-layer par...

The rotavirus A (RV-A) virions, known as triple-layer particles (TLPs), interact with the lumenal surface of enterocytes via their VP4 spikes that consist of cleaved VP4 fragments, VP8* and VP5*, and VP7, which forms the smooth surface of the TLP (reviewed in Desselberger 2014, Crawford et al. 2017, Suzuki 2019). Multiple host macromolecules associated with cell membrane lipid microdomains on the surface of enterocytes serve as RV-A receptors and co-receptors, such as sialoglycans (glycans that contain sialic acid - SA - at terminal or sub-terminal positions, e.g. gangliosides GM1 and GM1a), histo-blood group antigens (HBGAs), integrins (ITGA2:ITGB1, ITGA4:ITGB1, ITGAV:ITGB, and ITGAX:ITGB2), and HSPA8 (HSC70) (reviewed in Desselberger 2014, Crawford et al. 2017, Suzuki 2019, Amimo et al. 2021). Rotavirus interactions with HBGAs and sialoglycans are largely dependent on the rotavirus P genotype, which determines the amino acid sequence of VP4, and are related to host range restrictions and interspecies transmissibility of rotavirus strains (reviewed in Desselberger 2014, Crawford et al. 2017, Suzuki 2019). The P genotype also affects the mode of RV-A entry into host cells, where three different paths have been identified: direct penetration, clathrin-dependent, and clathrin-independent endocytosis, all resulting in release into the cytosol of RV-A double-layered particles (DLPs) (reviewed in Arias et al. 2015, Suzuki 2019). After endocytosis, depending on the viral strain, RV-A DLPs may enter the cytosol either from maturing or late endosomes (reviewed in Arias et al. 2015, Suzuki 2019). Studies of rotavirus entry into host cells have most often used the simian RV-A strain RRV (rhesus rotavirus) and African green monkey kidney cell line MA104 or the human colon carcinoma cell line Caco-2, which are model systems not representative of the in vivo infection process. Technical advances with 3D cultures of human intestinal enteroids promise to overcome this limitation of previous studies (Saxena et al. 2016).

In infants, human milk oligosaccharides, milk microbiome, and gut microbiome affect neonatal rotavirus infectivity (Ramani et al. 2018). The role of gut microbiota in rotavirus infection is reviewed in Amimo et al. 2021.