Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins

Sheng Fan Wang, Sung Pin Tseng, Chia Hung Yen, Jyh Yuan Yang, Ching Han Tsao, Chun Wei Shen, Kuan Hsuan Chen, Fu Tong Liu, Wu Tse Liu, Yi Ming Arthur Chen, Jason C. Huang

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37 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)208-214
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume451
Issue number2
DOIs
Publication statusPublished - Aug 22 2014
Externally publishedYes

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Keywords

  • Anti-spike antibody
  • Antibody-dependent enhancement
  • Fc receptors
  • HL-CZ
  • SARS-CoV

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Wang, S. F., Tseng, S. P., Yen, C. H., Yang, J. Y., Tsao, C. H., Shen, C. W., Chen, K. H., Liu, F. T., Liu, W. T., Chen, Y. M. A., & Huang, J. C. (2014). Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins. Biochemical and Biophysical Research Communications, 451(2), 208-214. https://doi.org/10.1016/j.bbrc.2014.07.090