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https://doi.org/10.1038/s41598-018-20305-4
Title: | Antibody-mediated enhancement aggravates chikungunya virus infection and disease severity |
Authors: | Lum, F.-M Couderc, T Chia, B.-S Ong, R.-Y Her, Z Chow, A Leo, Y.-S Kam, Y.-W Rénia, L Lecuit, M Ng, L.F.P |
Keywords: | Fc receptor Fc receptor IIa gamma interferon neutralizing antibody virus antibody animal arthralgia C57BL mouse cell culture chikungunya Chikungunya virus human immunology knockout mouse macrophage metabolism mouse pathology physiology severity of illness index virology virus load virus replication Animals Antibodies, Neutralizing Antibodies, Viral Arthralgia Cells, Cultured Chikungunya Fever Chikungunya virus Humans Interferon-gamma Macrophages Mice Mice, Inbred C57BL Mice, Knockout Receptors, IgG Severity of Illness Index Viral Load Virus Replication |
Issue Date: | 2018 |
Publisher: | Nature Publishing Group |
Citation: | Lum, F.-M, Couderc, T, Chia, B.-S, Ong, R.-Y, Her, Z, Chow, A, Leo, Y.-S, Kam, Y.-W, Rénia, L, Lecuit, M, Ng, L.F.P (2018). Antibody-mediated enhancement aggravates chikungunya virus infection and disease severity. Scientific Reports 8 (1) : 1860. ScholarBank@NUS Repository. https://doi.org/10.1038/s41598-018-20305-4 |
Abstract: | The arthropod-transmitted chikungunya virus (CHIKV) causes a flu-like disease that is characterized by incapacitating arthralgia. The re-emergence of CHIKV and the continual risk of new epidemics have reignited research in CHIKV pathogenesis. Virus-specific antibodies have been shown to control virus clearance, but antibodies present at sub-neutralizing concentrations can also augment virus infection that exacerbates disease severity. To explore this occurrence, CHIKV infection was investigated in the presence of CHIKV-specific antibodies in both primary human cells and a murine macrophage cell line, RAW264.7. Enhanced attachment of CHIKV to the primary human monocytes and B cells was observed while increased viral replication was detected in RAW264.7 cells. Blocking of specific Fc receptors (Fc?Rs) led to the abrogation of these observations. Furthermore, experimental infection in adult mice showed that animals had higher viral RNA loads and endured more severe joint inflammation in the presence of sub-neutralizing concentrations of CHIKV-specific antibodies. In addition, CHIKV infection in 11 days old mice under enhancing condition resulted in higher muscles viral RNA load detected and death. These observations provide the first evidence of antibody-mediated enhancement in CHIKV infection and pathogenesis and could also be relevant for other important arboviruses such as Zika virus. © 2018 The Author(s). |
Source Title: | Scientific Reports |
URI: | https://scholarbank.nus.edu.sg/handle/10635/174342 |
ISSN: | 2045-2322 |
DOI: | 10.1038/s41598-018-20305-4 |
Appears in Collections: | Elements Staff Publications |
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