title: Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins.
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.
authors: Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Sheng-Fan
authors: SF
authors: Wang
authors: Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Sung-Pin
authors: SP
authors: Tseng
authors: Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Chia-Hung
authors: CH
authors: Yen
authors: Center for Research, Diagnostics and Vaccine Development, Centers for Disease Control, Taipei, Taiwan.
authors: Jyh-Yuan
authors: JY
authors: Yang
authors: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors: Ching-Han
authors: CH
authors: Tsao
authors: Office of Occupational Safety and Health, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.
authors: Chun-Wei
authors: CW
authors: Shen
authors: Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Kuan-Hsuan
authors: KH
authors: Chen
authors: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors: Fu-Tong
authors: FT
authors: Liu
authors: Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Wu-Tse
authors: WT
authors: Liu
authors: Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Microbiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: arthur@kmu.edu.tw.
authors: Yi-Ming Arthur
authors: YM
authors: Chen
authors: Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan; AIDS Prevention and Research Center, National Yang-Ming University, Taipei, Taiwan. Electronic address: jchuang2@ym.edu.tw.
authors: Jason C
authors: JC
authors: Huang
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000914:Antibodies, Viral / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D000086462:Coronavirus Nucleocapsid Proteins; D003588:Cytopathogenic Effect, Viral; D006801:Humans; D019590:Nucleocapsid Proteins / Q000276:immunology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D045169:Severe Acute Respiratory Syndrome / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D064370:Spike Glycoprotein, Coronavirus / Q000276:immunology*; D014709:Vero Cells; D014765:Viral Vaccines / Q000276:immunology; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D000086462:Coronavirus Nucleocapsid Proteins; D019590:Nucleocapsid Proteins; D017452:Receptors, IgG; D011991:Receptors, Virus; D064370:Spike Glycoprotein, Coronavirus; D014765:Viral Vaccines; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2
keywords: Anti-spike antibody; Antibody-dependent enhancement; Fc receptors; HL-CZ; SARS-CoV