Antibody-mediated enhancement aggravates chikungunya virus infection and disease severity

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.

On the other hand, the intrinsic pathway typically results in increased virus entry and replication, often accompanied by the alterations of host immune responses 31, 32, [53] [54] [55] [56] (Fig. 8) . Intriguingly, enhanced CHIKV infection in murine RAW264.7 macrophages was even more prominent when the virus started replicating (6 hpi). Subsequently, this led to the high expression of several pro-inflammatory and anti-viral genes. This observation is enthralling as similar studies in DENV and RRV reported the down-regulation of these pro-inflammatory responses 31, 32, [53] [54] [55] [56] . While the data in this report differs, it opens up another compelling perspective in which enhanced CHIKV infection in susceptible cells can lead to augmented virus entry and replication, resulting in an active pro-inflammatory response from the infected cells (Fig. 8) . While the consequences of the elevated immune response remains to be investigate, it is plausible that CHIKV manipulates this immune outcome to its own advantage to achieve chronicity, as observed for other viral infections 57 .