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, 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
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.
Copyright © 2014 Elsevier Inc. All rights reserved.
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References
- Hsueh P.R., Yang P.C. SARS outbreak in Taiwan. Emerg. Infect. Dis. 2004;10:1514–1515. (author reply 1515–1516)
- Chang M.S., Lu Y.T., Ho S.T., Wu C.C., Wei T.Y., Chen C.J., Hsu Y.T., Chu P.C., Chen C.H., Chu J.M., Jan Y.L., Hung C.C., Fan C.C., Yang Y.C. Antibody detection of SARS-CoV spike and nucleocapsid protein. Biochem. Biophys. Res. Commun. 2004;314:931–936.
- Chen Y.M., Liang S.Y., Shih Y.P., Chen C.Y., Lee Y.M., Chang L., Jung S.Y., Ho M.S., Liang K.Y., Chen H.Y., Chan Y.J., Chu D.C. Epidemiological and genetic correlates of severe acute respiratory syndrome coronavirus infection in the hospital with the highest nosocomial infection rate in Taiwan in 2003. J. Clin. Microbiol. 2006;44:359–365.
- Li W., Moore M.J., Vasilieva N., Sui J., Wong S.K., Berne M.A., Somasundaran M., Sullivan J.L., Luzuriaga K., Greenough T.C., Choe H., Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426:450–454.
- Barnett S.W., Burke B., Sun Y., Kan E., Legg H., Lian Y., Bost K., Zhou F., Goodsell A., Zur Megede J., Polo J., Donnelly J., Ulmer J., Otten G.R., Miller C.J., Vajdy M., Srivastava I.K. Antibody-mediated protection against mucosal simian-human immunodeficiency virus challenge of macaques immunized with alphavirus replicon particles and boosted with trimeric envelope glycoprotein in MF59 adjuvant. J. Virol. 2010;84:5975–5985.
- Chen Z., Pei D., Jiang L., Song Y., Wang J., Wang H., Zhou D., Zhai J., Du Z., Li B., Qiu M., Han Y., Guo Z., Yang R. Antigenicity analysis of different regions of the severe acute respiratory syndrome coronavirus nucleocapsid protein. Clin. Chem. 2004;50:988–995.
- Tirado S.M., Yoon K.J. Antibody-dependent enhancement of virus infection and disease. Viral Immunol. 2003;16:69–86.
- Olsen C.W., Corapi W.V., Ngichabe C.K., Baines J.D., Scott F.W. Monoclonal antibodies to the spike protein of feline infectious peritonitis virus mediate antibody-dependent enhancement of infection of feline macrophages. J. Virol. 1992;66:956–965.
- Liu W.T., Chen C.L., Lee S.S., Chan C.C., Lo F.L., Ko Y.C. Isolation of dengue virus with a human promonocyte cell line. Am. J. Trop. Med. Hyg. 1991;44:494–499.
- Hsueh P.R., Hsiao C.H., Yeh S.H., Wang W.K., Chen P.J., Wang J.T., Chang S.C., Kao C.L., Yang P.C. Microbiologic characteristics, serologic responses, and clinical manifestations in severe acute respiratory syndrome, Taiwan. Emerg. Infect. Dis. 2003;9:1163–1167.
- Shih Y.P., Chen C.Y., Liu S.J., Chen K.H., Lee Y.M., Chao Y.C., Chen Y.M. Identifying epitopes responsible for neutralizing antibody and DC-SIGN binding on the spike glycoprotein of the severe acute respiratory syndrome coronavirus. J. Virol. 2006;80:10315–10324.
- Jiang S.S., Chen T.C., Yang J.Y., Hsiung C.A., Su I.J., Liu Y.L., Chen P.C., Juang J.L. Sensitive and quantitative detection of severe acute respiratory syndrome coronavirus infection by real-time nested polymerase chain reaction. Clin. Infect. Dis. 2004;38:293–296.
- Wang S.F., Huang J.C., Lee Y.M., Liu S.J., Chan Y.J., Chau Y.P., Chong P., Chen Y.M. DC-SIGN mediates avian H5N1 influenza virus infection in cis and in trans. Biochem. Biophys. Res. Commun. 2008;373:561–566.
- Wang S.F., Chen K.H., Thitithanyanont A., Yao L., Lee Y.M., Chan Y.J., Liu S.J., Chong P., Liu W.T., Huang J.C., Chen Y.M. Generating and characterizing monoclonal and polyclonal antibodies against avian H5N1 hemagglutinin protein. Biochem. Biophys. Res. Commun. 2009;382:691–696.
- Du A., Daidoji T., Koma T., Ibrahim M.S., Nakamura S., de Silva U.C., Ueda M., Yang C.S., Yasunaga T., Ikuta K., Nakaya T. Detection of circulating Asian H5N1 viruses by a newly established monoclonal antibody. Biochem. Biophys. Res. Commun. 2009;378:197–202.
- Jaume M., Yip M.S., Kam Y.W., Cheung C.Y., Kien F., Roberts A., Li P.H., Dutry I., Escriou N., Daeron M., Bruzzone R., Subbarao K., Peiris J.S., Nal B., Altmeyer R. SARS CoV subunit vaccine: antibody-mediated neutralisation and enhancement. Hong Kong Med. J. 2012;18(Suppl 2):31–36.
- Jaume M., Yip M.S., Cheung C.Y., Leung H.L., Li P.H., Kien F., Dutry I., Callendret B., Escriou N., Altmeyer R., Nal B., Daeron M., Bruzzone R., Peiris J.S. Anti-severe acute respiratory syndrome coronavirus spike antibodies trigger infection of human immune cells via a pH- and cysteine protease-independent FcgammaR pathway. J. Virol. 2011;85:10582–10597.
- Hamming I., Timens W., Bulthuis M.L., Lely A.T., Navis G., van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J. Pathol. 2004;203:631–637.
- Yilla M., Harcourt B.H., Hickman C.J., McGrew M., Tamin A., Goldsmith C.S., Bellini W.J., Anderson L.J. SARS-coronavirus replication in human peripheral monocytes/macrophages. Virus Res. 2005;107:93–101.
- Wang W., Ye L., Li B., Gao B., Zeng Y., Kong L., Fang X., Zheng H., Wu Z., She Y. Up-regulation of IL-6 and TNF-alpha induced by SARS-coronavirus spike protein in murine macrophages via NF-kappaB pathway. Virus Res. 2007;128:1–8.
- Yoshikawa T., Hill T., Li K., Peters C.J., Tseng C.T. Severe acute respiratory syndrome (SARS) coronavirus-induced lung epithelial cytokines exacerbate SARS pathogenesis by modulating intrinsic functions of monocyte-derived macrophages and dendritic cells. J. Virol. 2009;83:3039–3048.
- Park S., Sestak K., Hodgins D.C., Shoup D.I., Ward L.A., Jackwood D.J., Saif L.J. Immune response of sows vaccinated with attenuated transmissible gastroenteritis virus (TGEV) and recombinant TGEV spike protein vaccines and protection of their suckling pigs against virulent TGEV challenge exposure. Am. J. Vet. Res. 1998;59:1002–1008.
- Gollins S.W., Porterfield J.S. Flavivirus infection enhancement in macrophages: radioactive and biological studies on the effect of antibody on viral fate. J. Gen. Virol. 1984;65(Pt 8):1261–1272.
- Robinson W.E., Jr., Montefiori D.C., Gillespie D.H., Mitchell W.M. Complement-mediated, antibody-dependent enhancement of HIV-1 infection in vitro is characterized by increased protein and RNA syntheses and infectious virus release. J. Acquir. Immune Defic. Syndr. 1989;2:33–42.
- Olsen C., Scott F. Evaluation of antibody-dependent enhancement of feline infectious peritonitis virus infectivity using in situ hybridization. Microb. Pathog. 1993;14:275–285.
- Zhu M. SARS immunity and vaccination. Cell. Mol. Immunol. 2004;1:193–198.
- Kam Y.W., Kien F., Roberts A., Cheung Y.C., Lamirande E.W., Vogel L., Chu S.L., Tse J., Guarner J., Zaki S.R., Subbarao K., Peiris M., Nal B., Altmeyer R. Antibodies against trimeric S glycoprotein protect hamsters against SARS-CoV challenge despite their capacity to mediate FcgammaRII-dependent entry into B cells in vitro. Vaccine. 2007;25:729–740.
Source: PubMed