Intracellular neutralisation of rotavirus by VP6-specific IgG

Caddy, Sarah L, Vaysburd, Marina, Wing, Mark, Foss, Stian, Andersen, Jan Terje, O'Connell, Kevin, Mayes, Keith, Higginson, Katie, Iturriza-Gomara, Miren ORCID: 0000-0001-5816-6423, Desselberger, Ulrich
et al (show 1 more authors) (2020) Intracellular neutralisation of rotavirus by VP6-specific IgG. PLOS PATHOGENS, 16 (8). e1008732-.

Access the full-text of this item by clicking on the Open Access link.


Rotavirus is a major cause of gastroenteritis in children, with infection typically inducing high levels of protective antibodies. Antibodies targeting the middle capsid protein VP6 are particularly abundant, and as VP6 is only exposed inside cells, neutralisation must be post-entry. However, while a system of poly immune globulin receptor (pIgR) transcytosis has been proposed for anti-VP6 IgAs, the mechanism by which VP6-specific IgG mediates protection remains less clear. We have developed an intracellular neutralisation assay to examine how antibodies neutralise rotavirus inside cells, enabling comparison between IgG and IgA isotypes. Unexpectedly we found that neutralisation by VP6-specific IgG was much more efficient than by VP6-specific IgA. This observation was highly dependent on the activity of the cytosolic antibody receptor TRIM21 and was confirmed using an in vivo model of murine rotavirus infection. Furthermore, mice deficient in only IgG and not other antibody isotypes had a serious deficit in intracellular antibody-mediated protection. The finding that VP6-specific IgG protect mice against rotavirus infection has important implications for rotavirus vaccination. Current assays determine protection in humans predominantly by measuring rotavirus-specific IgA titres. Measurements of VP6-specific IgG may add to existing mechanistic correlates of protection.

Item Type: Article
Uncontrolled Keywords: Animals, Mice, Inbred BALB C, Mice, Inbred C57BL, Humans, Mice, Rotavirus, Rotavirus Infections, Immunoglobulin G, Capsid Proteins, Antibodies, Viral, Antigens, Viral, Species Specificity
Depositing User: Symplectic Admin
Date Deposited: 27 Aug 2020 13:52
Last Modified: 18 Jan 2023 23:36
DOI: 10.1371/journal.ppat.1008732
Open Access URL:
Related URLs: