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Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins
•The SARS coronavirus exhibits antibody-dependent enhancement (ADE).•SARS-CoV ADE is strongly mediated by anti-spike but not anti-nucleocapsid Abs.•Formerly untested HL-CZ cells are susceptible to SARS-CoV infection.•Highly diluted anti-sera against SARS-CoV enhances SARS-CoV infectivity. The severe...
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Published in: | Biochemical and biophysical research communications 2014-08, Vol.451 (2), p.208-214 |
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Main Authors: | , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | •The SARS coronavirus exhibits antibody-dependent enhancement (ADE).•SARS-CoV ADE is strongly mediated by anti-spike but not anti-nucleocapsid Abs.•Formerly untested HL-CZ cells are susceptible to SARS-CoV infection.•Highly diluted anti-sera against SARS-CoV enhances SARS-CoV infectivity.
The severe acute respiratory syndrome coronavirus (SARS-CoV) still carries the potential for reemergence, therefore efforts are being made to create a vaccine as a prophylactic strategy for control and prevention. Antibody-dependent enhancement (ADE) is a mechanism through which dengue viruses, feline coronaviruses, and HIV viruses take advantage of anti-viral humoral immune responses to infect host target cells. Here we describe our observations of SARS-CoV using ADE to enhance the infectivity of a HL-CZ human promonocyte cell line. Quantitative-PCR and immunofluorescence staining results indicate that SARS-CoV is capable of replication in HL-CZ cells, and of displaying virus-induced cytopathic effects and increased levels of TNF-α, IL-4 and IL-6 two days post-infection. According to flow cytometry data, the HL-CZ cells also expressed angiotensin converting enzyme 2 (ACE2, a SARS-CoV receptor) and higher levels of the FcγRII receptor. We found that higher concentrations of anti-sera against SARS-CoV neutralized SARS-CoV infection, while highly diluted anti-sera significantly increased SARS-CoV infection and induced higher levels of apoptosis. Results from infectivity assays indicate that SARS-CoV ADE is primarily mediated by diluted antibodies against envelope spike proteins rather than nucleocapsid proteins. We also generated monoclonal antibodies against SARS-CoV spike proteins and observed that most of them promoted SARS-CoV infection. Combined, our results suggest that antibodies against SARS-CoV spike proteins may trigger ADE effects. The data raise new questions regarding a potential SARS-CoV vaccine, while shedding light on mechanisms involved in SARS pathogenesis. |
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ISSN: | 0006-291X 1090-2104 |
DOI: | 10.1016/j.bbrc.2014.07.090 |