SARS coronavirus has antibody-dependent enhancement (ADE) effect through the autologous antibodies against envelope spikes on Fcγ receptor expressing cells
Supplement : Abstracts of the 2016 International Symposium on HIV and Emerging Infectious Diseases (ISHEID)Journal of Virus Eradication 2016; 2 supplement 1
Abstract No : P84
Chun-Sheng Yeh1,2, Jyh-Yuan Yang4, Wu-Tse Liu5, Jason C. Huang5,6, Yi-Ming Arthur Chen2,3, Sheng-Fan Wang1,2
1Kaohsiung Medical University, Department of Medical Laboratory Science and Biotechnology, Kaohsiung, Taiwan, 2Kaohsiung Medical University, Center for Infectious Disease and Cancer Research, Kaohsiung, Taiwan, 3Kaohsiung Medical University, College of Medicine, Department of Microbiology, Kaohsiung, Taiwan, 4Center for Research, Diagnostics and Vaccine Development, Centers for Disease Control, Taipei, Taiwan, 5National Yang-Ming University, Department of Biotechnology and Laboratory Science in Medicine, Taipei, Taiwan, 6National Yang-Ming University, AIDS Prevention and Research Center, Taipei, Taiwan
Background: Severe acute respiratory syndrome coronavirus (SARS-CoV) had an outbreak in 2003. Even though SARS-CoV now remains in the natural bat reservoir, it still has the reemergence threat. Vaccination is a prophylactic strategy for this disease control and prevention. Antibody-dependent enhancement (ADE) is a mechanism by which viruses such as, dengue virus, feline coronavirus, and HIV, as alternative strategies, apply to infect host cells to gain entry into the target cells by taking advantage of anti-viral humoral immune responses. The ADE effect of SARS-CoV infection is controversial.
Materials: SARS-CoV TW1 strain (GenBank accession no., AY291451) was obtained from Taiwan CDC and SARS-CoV pseudotyped virus particles harboring the SARS-CoV S protein with HIV core structure virus were constructed for infectivity assay. The anti-SARS CoV infected patient's sera and generated monoclonal and polyclonal antibodies against spike proteins were used for infectivity and neutralization assay. Immunofluorescence staining and transmission electron microscopy observation were performed to assay the viral susceptibility and ADE on HL-CZ cells with SASR-CoV infection in the presence of the different dilutions of anti-sera against SARS-CoV.
Results: We found that SARS-CoV uses ADE to enhance its infectivity towards a human promonocyte cell line-HL-CZ. Quantitative-PCR and immunofluorescent staining indicated that SARS-CoV can replicate in HL-CZ and display virus-induced cytopathic effect as well as increased TNF-α, IL-4 and IL-6 two days postinfection. Results from flow-cytometry indicate HL-CZ cells express angiotensin converting enzyme 2 (ACE2), a SARS-CoV receptors and higher level of FcrRII receptors. Our data demonstrated that higher diluted sera from SARS-CoV infection patients promote SARS-CoV infection and induced higher level of apoptosis. Infectivity assay demonstrated that ADE of SARS-CoV is majorly mediated by diluted antibodies against envelope spikes rather than nucleocapsid proteins. We further generated monoclonal antibodies against spike proteins of SARS-CoV and found that most monoclonal antibodies promote SARS-CoV infection.
Conclusions: We suggested that antibodies against spike proteins of SARS-CoV may cause ADE effect. This data raises reasonable concern regarding the use of SARS-CoV vaccine and shed light on some roles in SARS pathogenesis.