Antibody-mediated enhancement aggravates chikungunya virus infection and disease severity

Fok-Moon Lum (Lead / Corresponding author), Thérèse Couderc, Bing-Shao Chia, Ruo-Yan Ong, Zhisheng Her, Angela Chow, Yee-Sin Leo, Yiu-Wing Kam, Laurent Rénia, Marc Lecuit, Lisa F. P. Ng (Lead / Corresponding author)

Research output: Contribution to journalArticle

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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 (FcγRs) 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.

Original languageEnglish
Article number1860
Pages (from-to)1-14
Number of pages14
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 30 Jan 2018

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Chikungunya virus
Virus Diseases
Antibodies
Viral RNA
Viral Load
Viruses
Arboviruses
Fc Receptors
Arthropods
Arthralgia
Chikungunya Fever
Monocytes
B-Lymphocytes
Joints
Macrophages
Inflammation
Cell Line
Muscles
Infection
Research

Keywords

  • Journal article
  • Infection
  • Viral infection

Cite this

Lum, Fok-Moon ; Couderc, Thérèse ; Chia, Bing-Shao ; Ong, Ruo-Yan ; Her, Zhisheng ; Chow, Angela ; Leo, Yee-Sin ; Kam, Yiu-Wing ; Rénia, Laurent ; Lecuit, Marc ; Ng, Lisa F. P. / Antibody-mediated enhancement aggravates chikungunya virus infection and disease severity. In: Scientific Reports. 2018 ; Vol. 8, No. 1. pp. 1-14.
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title = "Antibody-mediated enhancement aggravates chikungunya virus infection and disease severity",
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 (FcγRs) 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.",
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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, LFP 2018, 'Antibody-mediated enhancement aggravates chikungunya virus infection and disease severity', Scientific Reports, vol. 8, no. 1, 1860, pp. 1-14. https://doi.org/10.1038/s41598-018-20305-4

Antibody-mediated enhancement aggravates chikungunya virus infection and disease severity. / Lum, Fok-Moon (Lead / Corresponding author); Couderc, Thérèse; Chia, Bing-Shao; Ong, Ruo-Yan; Her, Zhisheng; Chow, Angela; Leo, Yee-Sin; Kam, Yiu-Wing; Rénia, Laurent; Lecuit, Marc; Ng, Lisa F. P. (Lead / Corresponding author).

In: Scientific Reports, Vol. 8, No. 1, 1860, 30.01.2018, p. 1-14.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Antibody-mediated enhancement aggravates chikungunya virus infection and disease severity

AU - Lum, Fok-Moon

AU - Couderc, Thérèse

AU - Chia, Bing-Shao

AU - Ong, Ruo-Yan

AU - Her, Zhisheng

AU - Chow, Angela

AU - Leo, Yee-Sin

AU - Kam, Yiu-Wing

AU - Rénia, Laurent

AU - Lecuit, Marc

AU - Ng, Lisa F. P.

N1 - This project was funded in part by the EU project FP7-ICRES (grant no. 261202), and LabEx IBEID, Institut Pasteur and Inserm

PY - 2018/1/30

Y1 - 2018/1/30

N2 - 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 (FcγRs) 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.

AB - 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 (FcγRs) 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.

KW - Journal article

KW - Infection

KW - Viral infection

U2 - 10.1038/s41598-018-20305-4

DO - 10.1038/s41598-018-20305-4

M3 - Article

VL - 8

SP - 1

EP - 14

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 1860

ER -