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Journal of Virology, November 2006, p. 10692-10699, Vol. 80, No. 21
0022-538X/06/$08.00+0     doi:10.1128/JVI.00927-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Rotavirus Anti-VP6 Secretory Immunoglobulin A Contributes to Protection via Intracellular Neutralization but Not via Immune Exclusion{dagger} ,{triangledown}

Blaise Corthésy,1 Yann Benureau,2 Clémentine Perrier,1 Cynthia Fourgeux,2 Nathalie Parez,3,4 Harry Greenberg,5,6 and Isabelle Schwartz-Cornil2*

R & D Laboratory of the Division of Immunology and Allergy, DMI-CHUV, Rue du Bugnon, 1011 Lausanne, Switzerland,1 Virologie et Immunologie Moléculaires UR892 INRA, Domaine de Vilvert, 78352 Jouy-en-Josas Cedex, France,2 Service des Urgences Médicales Pédiatriques, Hôpital Armand Trousseau AP-HP, Paris, France,3 Laboratoire de Virologie, EA 3500, UFR Saint Antoine, UMPC, Paris, France,4 Departments of Medicine and Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305,5 Palo Alto V.A. Health Care System, Palo Alto, California 943056

Received 5 May 2006/ Accepted 18 August 2006

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.

* Corresponding author. Mailing address: Virologie et Immunologie Moléculaires UR892 INRA, Domaine de Vilvert, 78352 Jouy-en-Josas Cedex, France. Phone: 33-134652641. Fax: 33-134652621. E-mail: isabelle.schwartz{at}jouy.inra.fr.

{dagger} This work is dedicated to the memory of Jean Cohen.

{triangledown} Published ahead of print on 6 September 2006.

Journal of Virology, November 2006, p. 10692-10699, Vol. 80, No. 21
0022-538X/06/$08.00+0     doi:10.1128/JVI.00927-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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