Please use this identifier to cite or link to this item: 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
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