Peste des Petits Ruminants Virus Fusion and Hemagglutinin Proteins Trigger Antibody-Dependent Cell-Mediated Cytotoxicity in Infected Cells

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Abstract

The adaptive immune system utilizes multiple effector mechanisms to clear viral infections. Among those antibody-dependent cell-mediated cytotoxicity (ADCC) can help recognize and clear virus-infected cells. In the present work we evaluated ADCC contribution to immunity in two economically important viral diseases that affect ruminants: bluetongue and peste des petits ruminants. Immune sera obtained from sheep experimentally infected with bluetongue virus (BTV) serotype 8 or peste des petits ruminant virus (PPRV) IC'89 were used for this study. PPRV immune sera could bind to the surface of PPRV-infected ovine B cells while BTV immune sera was unable to bind to the surface of BTV-infected sheep cells but could recognize intracellular BTV antigens. BTV and PPRV immune serum ADCC potency was established using an ovine autologous cytotoxicity assay that employed an NK cell-enriched fraction as effector cells and a virus-infected B cell-enriched fraction as target cells. In this system, immune sera triggered ADCC against PPRV-infected cells, but not against BTV-infected cells. PPRV immune sera could recognize PPRV fusion and hemagglutinin proteins on the surface of transfected cells, and enhanced lysis of these cells in ADCC assays. This indicated that these viral antigens are natural ADCC targets during PPRV infection. The present work describes a novel effector immune mechanism against PPRV in the natural host that could contribute to virus clearance highlighting the importance of studying protective immune mechanisms to improve current vaccines by invoking all effector arms of immunity.

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A novel role for non-neutralizing antibodies against nucleoprotein in facilitating resistance to influenza virus.

Amy Moquin, D. Kaminski, Damian M. Carragher … (2008)

Current influenza vaccines elicit Abs to the hemagglutinin and neuraminidase envelope proteins. Due to antigenic drift, these vaccines must be reformulated annually to include the envelope proteins predicted to dominate in the following season. By contrast, vaccination with the conserved nucleoprotein (NP) elicits immunity against multiple serotypes (heterosubtypic immunity). NP vaccination is generally thought to convey protection primarily via CD8 effector mechanisms. However, significant titers of anti-NP Abs are also induced, yet the involvement of Abs in protection has largely been disregarded. To investigate how Ab responses might contribute to heterosubtypic immunity, we vaccinated C57BL/6 mice with soluble rNP. This approach induced high titers of NP-specific serum Ab, but only poorly detectable NP-specific T cell responses. Nevertheless, rNP immunization significantly reduced morbidity and viral titers after influenza challenge. Importantly, Ab-deficient mice were not protected by this vaccination strategy. Furthermore, rNP-immune serum could transfer protection to naive hosts in an Ab-dependent manner. Therefore, Ab to conserved, internal viral proteins, such as NP, provides an unexpected, yet important mechanism of protection against influenza. These results suggest that vaccines designed to elicit optimal heterosubtypic immunity to influenza should promote both Ab and T cell responses to conserved internal proteins.

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Antibody-dependent cellular cytotoxicity is associated with control of pandemic H1N1 influenza virus infection of macaques.

Sinthujan Jegaskanda, Jason T Weinfurter, T. Friedrich … (2013)

Emerging influenza viruses pose a serious risk to global human health. Recent studies in ferrets, macaques, and humans suggest that seasonal H1N1 (sH1N1) infection provides some cross-protection against 2009 pandemic influenza viruses (H1N1pdm), but the correlates of cross-protection are poorly understood. Here we show that seasonal infection of influenza-naïve Indian rhesus macaques (Macaca mulatta) with A/Kawasaki/173/2001 (sH1N1) virus induces antibodies capable of binding the hemagglutinin (HA) of both the homologous seasonal virus and the antigenically divergent A/California/04/2009 (H1N1pdm) strain in the absence of detectable H1N1pdm-specific neutralizing antibodies. These influenza virus-specific antibodies activated macaque NK cells to express both CD107a and gamma interferon (IFN-γ) in the presence of HA proteins from either sH1N1 or H1N1pdm viruses. Although influenza virus-specific antibody-dependent cellular cytotoxicity (ADCC)-mediated NK cell activation diminished in titer over time following sH1N1 infection, these cells expanded rapidly within 7 days following H1N1pdm exposure. Furthermore, we found that influenza virus-specific ADCC was present in bronchoalveolar lavage fluid and was able to activate lung NK cells. We concluded that infection with a seasonal influenza virus can induce antibodies that mediate ADCC capable of recognizing divergent influenza virus strains. Cross-reactive ADCC may provide a mechanism for reducing the severity of divergent influenza virus infections.

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Contributions of antinucleoprotein IgG to heterosubtypic immunity against influenza virus.

Mark LaMere, Ho-Tak Lam, Amy Moquin … (2011)

Influenza A virus causes recurring seasonal epidemics and occasional influenza pandemics. Because of changes in envelope glycoprotein Ags, neutralizing Abs induced by inactivated vaccines provide limited cross-protection against new viral serotypes. However, prior influenza infection induces heterosubtypic immunity that accelerates viral clearance of a second strain, even if the external proteins are distinct. In mice, cross-protection can also be elicited by systemic immunization with the highly conserved internal nucleoprotein (NP). Both T lymphocytes and Ab contribute to such cross-protection. In this paper, we demonstrate that anti-NP IgG specifically promoted influenza virus clearance in mice by using a mechanism involving both FcRs and CD8(+) cells. Furthermore, anti-NP IgG rescued poor heterosubtypic immunity in B cell-deficient mice, correlating with enhanced NP-specific CD8 T cell responses. Thus, Ab against this conserved Ag has potent antiviral activity both in naive and in influenza-immune subjects. Such antiviral activity was not seen when mice were vaccinated with another internal influenza protein, nonstructural 1. The high conservation of NP Ag and the known longevity of Ab responses suggest that anti-NP IgG may provide a critically needed component of a universal influenza vaccine.

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Author and article information

Contributors

José M. Rojas: URI : http://loop.frontiersin.org/people/523081/overview

Verónica Martín: URI : http://loop.frontiersin.org/people/524923/overview

Noemí Sevilla: URI : http://loop.frontiersin.org/people/44975/overview

Journal

Journal ID (nlm-ta): Front Immunol

Journal ID (iso-abbrev): Front Immunol

Journal ID (publisher-id): Front. Immunol.

Title: Frontiers in Immunology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1664-3224

Publication date (Electronic): 14 January 2019

Publication date Collection: 2018

Volume: 9

Electronic Location Identifier: 3172

Affiliations

Centro de Investigación en Sanidad Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (CISA-INIA) , Madrid, Spain

Author notes

Edited by: Fabrizio Ceciliani, University of Milan, Italy

Reviewed by: Jayne Hope, University of Edinburgh, United Kingdom; Sara Louise Cosby, Queen's University Belfast, United Kingdom; Hinh Ly, University of Minnesota Twin Cities, United States

*Correspondence: Noemí Sevilla sevilla@ 123456inia.es

This article was submitted to Comparative Immunology, a section of the journal Frontiers in Immunology

Article

DOI: 10.3389/fimmu.2018.03172

PMC ID: 6339941

PubMed ID: 30693004

SO-VID: e3786af0-f8f8-4ee2-b154-101aaab67246

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 31 August 2018

Date accepted : 24 December 2018

Page count

Figures: 5, Tables: 0, Equations: 0, References: 47, Pages: 11, Words: 7584

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Peste des Petits Ruminants Virus Fusion and Hemagglutinin Proteins Trigger Antibody-Dependent Cell-Mediated Cytotoxicity in Infected Cells

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Abstract

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Gamma Delta T cells

Most cited references 38

A novel role for non-neutralizing antibodies against nucleoprotein in facilitating resistance to influenza virus.

Antibody-dependent cellular cytotoxicity is associated with control of pandemic H1N1 influenza virus infection of macaques.

Contributions of antinucleoprotein IgG to heterosubtypic immunity against influenza virus.

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Cited by 6

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