Antibody-mediated enhancement aggravates chikungunya virus infection and disease severity

Fok-Moon Lum (1, 2) , Thérèse Couderc (3) , Bing-Shao Chia (2) , Ruo-Yan Ong (2) , Zhisheng Her (2) , Angela Chow (4) , Yee-Sin Leo (4) , Yiu-Wing Kam (2) , Laurent Rénia (2) , Marc Lecuit (3, 5, 6, 7) , Lisa Ng (8, 2, 1)

1 Yong Loo Lin School of Medicine [Singapore]
2 A*STAR - Agency for science, technology and research [Singapore]
3 Biologie des Infections - Biology of Infection
4 Institute of Infectious Diseases and Epidemiology [Singapore, Singapore]
5 UPD5 - Université Paris Descartes - Paris 5
6 CHU Necker - Enfants Malades [AP-HP]
7 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
8 University of Liverpool

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.

Domains: Human health and pathology; Infectious diseases; Emerging diseases; Microbiology and Parasitology; Virology; Immunology

Fok-Moon Lum, Thérèse Couderc, Bing-Shao Chia, Ruo-Yan Ong, Zhisheng Her, et al.. Antibody-mediated enhancement aggravates chikungunya virus infection and disease severity. Scientific Reports, 2018, 8 (1), pp.1860. ⟨10.1038/s41598-018-20305-4⟩. ⟨pasteur-02185035⟩