Investigation of Antibody-Dependent Enhancement (ADE) of SARS coronavirus infection and its role in pathogenesis of SARS
© Yip et al; licensee BioMed Central Ltd. 2011
Published: 10 January 2011
Antibody-dependent enhancement (ADE) is a mechanism by which viruses, such as dengue, HIV and Ebola, gain entry into some target cells through the use of host antiviral humoral immune responses . Here, we studied the ability of severe acute respiratory syndrome coronavirus (SARS-CoV)  to use ADE mechanisms to enhance its infectivity towards cells of the hematopoietic lineage.
We found that heat-inactivated immune serum from rodents vaccinated with recombinant native full-length Spike protein trimers  triggered infection of human immune cells (monocytic and B cell lines) by SARS-CoV Spike pseudotyped particle (SARS-CoVpp). The occurrence of antibody-mediated infection of human Raji B cells was further investigated by using live SARS-CoV. Similarly to results obtained with the SARS-CoVpp, only anti-SARS-CoV Spike serum, but not mock immune-serum, induced a massive increase of SARS-CoV viral genes (ORF1b and Nucleocapsid) and viral proteins (Membrane and Nucleocapsid) in Raji B cells. As revealed by immunostaining, only a relatively low, however significant percentage of the Raji cells get infected by antibody-mediated infection and did not allow direct assessment of productive replication by conventional cytopathic assays and TCID50 titration.
Taken together, our data suggested that SARS-CoV is able to enter human immune cells via an antibody-mediated pathway and immunological consequences of such infection are under investigation (productive replication, cytokines secretion profile and cell death etc). Our data raise reasonable concerns regarding the use of SARS-CoV vaccine in humans and pave the way to further studies focusing on the role of immune-mediated infection phenomenon during SARS pathogenesis.
- Takada A, Kawaoka Y: Antibody-dependent enhancement of viral infection: molecular mechanisms and in vivo implications. Rev Med Virol. 2003, 13: 387-398. 10.1002/rmv.405.View ArticlePubMedGoogle Scholar
- Du L, He Y, Zhou Y, Liu S, Zheng BJ, Jiang S: The spike protein of SARS-CoV--a target for vaccine and therapeutic development. Nat Rev Microbiol. 2009, 3: 226-236. 10.1038/nrmicro2090.View ArticleGoogle Scholar
- Kam YW, Kien F, Roberts A, Cheung YC, Lamirande EW, Vogel L, Chu SL, Tse J, Guarner J, Zaki SR, 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. 10.1016/j.vaccine.2006.08.011.View ArticlePubMedGoogle Scholar
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