Rotavirus anti-VP6 secretory immunoglobulin A contributes to protection via intracellular neutralization but not via immune exclusion.

Details

Serval ID
serval:BIB_03D399D255B4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Rotavirus anti-VP6 secretory immunoglobulin A contributes to protection via intracellular neutralization but not via immune exclusion.
Journal
Journal of Virology
Author(s)
Corthésy B., Benureau Y., Perrier C., Fourgeux C., Parez N., Greenberg H., Schwartz-Cornil I.
ISSN
0022-538X[print], 0022-538X[linking]
Publication state
Published
Issued date
2006
Volume
80
Number
21
Pages
10692-10699
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Immunoglobulin A (IgA) monoclonal antibodies (MAbs) directed at the conserved inner core protein VP6 of rotavirus, such as the IgA7D9 MAb, provide protective immunity in adult and suckling mice when delivered systemically. While these antibodies do not have traditional in vitro neutralizing activity, they could mediate their antiviral activity either by interfering with the viral replication cycle along the IgA secretory pathway or by acting at mucosal surfaces as secretory IgA and excluding virus from target enterocytes. We sought to determine the critical step at which antirotaviral activity was initiated by the IgA7D9 MAb. The IgA7D9 MAb appeared to directly interact with purified triple-layer viral particles, as shown by immunoprecipitation and immunoblotting. However, protection was not conferred by passively feeding mice with the secretory IgA7D9 MAb. This indicates that the secretory IgA7D9 MAb does not confer protection by supplying immune exclusion activity in vivo. We next evaluated the capacity of polymeric IgA7D9 MAb to neutralize rotavirus intracellularly during transcytosis. We found that when polymeric IgA7D9 MAb was applied to the basolateral pole of polarized Caco-2 intestinal cells, it significantly reduced viral replication and prevented the loss of barrier function induced by apical exposure of the cell monolayer to rotavirus, supporting the conclusion that the antibody carries out its antiviral activity intracellularly. These findings identify a mechanism whereby the well-conserved immunodominant VP6 protein can function as a target for heterotypic antibodies and protective immunity.
Keywords
Animals, Antibodies, Monoclonal/pharmacology, Antibodies, Viral/pharmacology, Antigens, Viral/immunology, Caco-2 Cells, Capsid Proteins/immunology, Humans, Immunoglobulin A, Secretory/pharmacology, Intestines/immunology, Intestines/virology, Mice, Mice, Inbred BALB C, Neutralization Tests, Rotavirus/immunology, Rotavirus/pathogenicity, Rotavirus Infections/immunology, Rotavirus Infections/therapy, Virus Replication/immunology
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 14:53
Last modification date
20/08/2019 12:25
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