Understanding internalization of rotavirus VP6 nanotubes by cells: towards a recombinant vaccine
Por:
Rodríguez M., Wood C., Sanchez-López R., Castro-Acosta R.M., Ramírez O.T., Palomares L.A.
Publicada:
1 may 2014
Categoría:
Virology
Resumen:
Rotavirus VP6 nanotubes are an attractive option for a recombinant
vaccine against rotavirus disease. Protection against rotavirus
infection and an adjuvant effect have been observed upon immunization
with VP6 nanotubes. However, little information exists on how VP6
nanotubes interact with cells and trigger an immune response. In this
work, the interaction between VP6 nanotubes and different cell lines was
characterized. VP6 nanotubes were not cytotoxic to any of the animal or
human cell lines tested. Uptake of nanotubes into cells was
cell-line-dependent, as only THP1 and J774 macrophage cells internalized
them. Moreover, the size and spatial arrangement of VP6 assembled into
nanotubes allowed their uptake by macrophages, as double-layered
rotavirus-like particles also displaying VP6 in their surface were not
taken up. The internalization of VP6 nanotubes was inhibited by
methyl-beta-cyclodextrin, but not by genistein, indicating that nanotube
entry is specific, depends on the presence of cholesterol in the plasma
membrane, and does not require the activity of tyrosine kinases. The
information generated here expands our understanding of the interaction
of protein nanotubes with cells, which is useful for the application of
VP6 nanotubes as a vaccine.
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