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Article: Anti-severe acute respiratory syndrome coronavirus spike antibodies trigger infection of human immune cells via a pH- and cysteine protease-independent Fcγr pathway

TitleAnti-severe acute respiratory syndrome coronavirus spike antibodies trigger infection of human immune cells via a pH- and cysteine protease-independent Fcγr pathway
Authors
Issue Date2011
PublisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/
Citation
Journal Of Virology, 2011, v. 85 n. 20, p. 10582-10597 How to Cite?
AbstractPublic health measures successfully contained outbreaks of the severe acute respiratory syndrome coronavirus (SARS-CoV) infection. However, the precursor of the SARS-CoV remains in its natural bat reservoir, and reemergence of a human-adapted SARS-like coronavirus remains a plausible public health concern. Vaccination is a major strategy for containing resurgence of SARS in humans, and a number of vaccine candidates have been tested in experimental animal models. We previously reported that antibody elicited by a SARS-CoV vaccine candidate based on recombinant full-length Spike-protein trimers potentiated infection of human B cell lines despite eliciting in vivo a neutralizing and protective immune response in rodents. These observations prompted us to investigate the mechanisms underlying antibody-dependent enhancement (ADE) of SARS-CoV infection in vitro. We demonstrate here that anti-Spike immune serum, while inhibiting viral entry in a permissive cell line, potentiated infection of immune cells by SARS-CoV Spike-pseudotyped lentiviral particles, as well as replication-competent SARS coronavirus. Antibody-mediated infection was dependent on Fcγ receptor II but did not use the endosomal/lysosomal pathway utilized by angiotensin I converting enzyme 2 (ACE2), the accepted receptor for SARS-CoV. This suggests that ADE of SARS-CoV utilizes a novel cell entry mechanism into immune cells. Different SARS vaccine candidates elicit sera that differ in their capacity to induce ADE in immune cells despite their comparable potency to neutralize infection in ACE2-bearing cells. Our results suggest a novel mechanism by which SARS-CoV can enter target cells and illustrate the potential pitfalls associated with immunization against it. These findings should prompt further investigations into SARS pathogenesis. © 2011, American Society for Microbiology.
Persistent Identifierhttp://hdl.handle.net/10722/142316
ISSN
2015 Impact Factor: 4.606
2015 SCImago Journal Rankings: 3.347
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Government05050182
09080872
Institut Pasteur International Network
GlaxoSmithKline Biologicals
Funding Information:

This study was supported by the Research Fund for the Control of Infectious Disease (projects 05050182 and 09080872) of the Hong Kong Government, by the RESPARI project of the Institut Pasteur International Network, and in part by grants from GlaxoSmithKline Biologicals. B. C. was supported by a fellowship from GlaxoSmithKline Biologicals.

References

 

DC FieldValueLanguage
dc.contributor.authorJaume, Men_HK
dc.contributor.authorYip, MSen_HK
dc.contributor.authorCheung, CYen_HK
dc.contributor.authorLeung, HLen_HK
dc.contributor.authorLi, PHen_HK
dc.contributor.authorKien, Fen_HK
dc.contributor.authorDutry, Ien_HK
dc.contributor.authorCallendret, Ben_HK
dc.contributor.authorEscriou, Nen_HK
dc.contributor.authorAltmeyer, Ren_HK
dc.contributor.authorNal, Ben_HK
dc.contributor.authorDaëron, Men_HK
dc.contributor.authorBruzzone, Ren_HK
dc.contributor.authorPeiris, JSMen_HK
dc.date.accessioned2011-10-28T02:42:46Z-
dc.date.available2011-10-28T02:42:46Z-
dc.date.issued2011en_HK
dc.identifier.citationJournal Of Virology, 2011, v. 85 n. 20, p. 10582-10597en_HK
dc.identifier.issn0022-538Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/142316-
dc.description.abstractPublic health measures successfully contained outbreaks of the severe acute respiratory syndrome coronavirus (SARS-CoV) infection. However, the precursor of the SARS-CoV remains in its natural bat reservoir, and reemergence of a human-adapted SARS-like coronavirus remains a plausible public health concern. Vaccination is a major strategy for containing resurgence of SARS in humans, and a number of vaccine candidates have been tested in experimental animal models. We previously reported that antibody elicited by a SARS-CoV vaccine candidate based on recombinant full-length Spike-protein trimers potentiated infection of human B cell lines despite eliciting in vivo a neutralizing and protective immune response in rodents. These observations prompted us to investigate the mechanisms underlying antibody-dependent enhancement (ADE) of SARS-CoV infection in vitro. We demonstrate here that anti-Spike immune serum, while inhibiting viral entry in a permissive cell line, potentiated infection of immune cells by SARS-CoV Spike-pseudotyped lentiviral particles, as well as replication-competent SARS coronavirus. Antibody-mediated infection was dependent on Fcγ receptor II but did not use the endosomal/lysosomal pathway utilized by angiotensin I converting enzyme 2 (ACE2), the accepted receptor for SARS-CoV. This suggests that ADE of SARS-CoV utilizes a novel cell entry mechanism into immune cells. Different SARS vaccine candidates elicit sera that differ in their capacity to induce ADE in immune cells despite their comparable potency to neutralize infection in ACE2-bearing cells. Our results suggest a novel mechanism by which SARS-CoV can enter target cells and illustrate the potential pitfalls associated with immunization against it. These findings should prompt further investigations into SARS pathogenesis. © 2011, American Society for Microbiology.en_HK
dc.languageengen_US
dc.publisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/en_HK
dc.relation.ispartofJournal of Virologyen_HK
dc.rightsJournal of Virology. Copyright © American Society for Microbiology.-
dc.rightsCopyright © American Society for Microbiology, [Journal of Virology, 2011, v. 85 n. 20, p. 10582-10597]-
dc.subject.meshAntibodies, Viral - metabolism-
dc.subject.meshAntibody-Dependent Enhancement-
dc.subject.meshLymphocytes - virology-
dc.subject.meshMembrane Glycoproteins - metabolism-
dc.subject.meshReceptors, IgG - metabolism-
dc.titleAnti-severe acute respiratory syndrome coronavirus spike antibodies trigger infection of human immune cells via a pH- and cysteine protease-independent Fcγr pathwayen_HK
dc.typeArticleen_HK
dc.identifier.emailCheung, CY: chungey@hkucc.hku.hken_HK
dc.identifier.emailNal, B: bnal@hkucc.hku.hken_HK
dc.identifier.emailBruzzone, R: bruzzone@hkucc.hku.hken_HK
dc.identifier.emailPeiris, JSM: malik@hkucc.hku.hken_HK
dc.identifier.authorityCheung, CY=rp00404en_HK
dc.identifier.authorityNal, B=rp00541en_HK
dc.identifier.authorityBruzzone, R=rp01442en_HK
dc.identifier.authorityPeiris, JSM=rp00410en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1128/JVI.00671-11en_HK
dc.identifier.pmid21775467-
dc.identifier.pmcidPMC3187504-
dc.identifier.scopuseid_2-s2.0-80055012547en_HK
dc.identifier.hkuros196721en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80055012547&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume85en_HK
dc.identifier.issue20en_HK
dc.identifier.spage10582en_HK
dc.identifier.epage10597en_HK
dc.identifier.isiWOS:000296254100015-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridJaume, M=6603007958en_HK
dc.identifier.scopusauthoridYip, MS=54397823800en_HK
dc.identifier.scopusauthoridCheung, CY=7202061836en_HK
dc.identifier.scopusauthoridLeung, HL=54397398600en_HK
dc.identifier.scopusauthoridLi, PH=15127492900en_HK
dc.identifier.scopusauthoridKien, F=7004231633en_HK
dc.identifier.scopusauthoridDutry, I=54396851000en_HK
dc.identifier.scopusauthoridCallendret, B=25121431500en_HK
dc.identifier.scopusauthoridEscriou, N=6603606703en_HK
dc.identifier.scopusauthoridAltmeyer, R=7003677186en_HK
dc.identifier.scopusauthoridNal, B=6506672380en_HK
dc.identifier.scopusauthoridDaëron, M=7005773227en_HK
dc.identifier.scopusauthoridBruzzone, R=7006793327en_HK
dc.identifier.scopusauthoridPeiris, JSM=7005486823en_HK

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