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

Biochem Biophys Res Commun. 2014 Aug 22;451(2):208-14. doi: 10.1016/j.bbrc.2014.07.090. Epub 2014 Jul 26.

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.

Keywords: Anti-spike antibody; Antibody-dependent enhancement; Fc receptors; HL-CZ; SARS-CoV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / metabolism*
  • Cell Line
  • Chlorocebus aethiops
  • Cytopathogenic Effect, Viral
  • Humans
  • Nucleocapsid Proteins / immunology
  • Peptidyl-Dipeptidase A / metabolism
  • Receptors, IgG / metabolism
  • Receptors, Virus / metabolism
  • SARS Virus / immunology*
  • SARS Virus / pathogenicity
  • SARS Virus / physiology
  • Severe Acute Respiratory Syndrome / etiology
  • Severe Acute Respiratory Syndrome / immunology*
  • Severe Acute Respiratory Syndrome / prevention & control
  • Spike Glycoprotein, Coronavirus / immunology*
  • Vero Cells
  • Viral Vaccines / immunology
  • Virus Replication

Substances

  • Antibodies, Viral
  • Nucleocapsid Proteins
  • Receptors, IgG
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • Viral Vaccines
  • nucleocapsid protein, Coronavirus
  • Peptidyl-Dipeptidase A
  • angiotensin converting enzyme 2