Infection and activation of human peripheral blood monocytes by dengue viruses through the mechanism of antibody-dependent enhancement

Abstract

Human monocytes are susceptible to dengue virus (DV) infection through an FcR-dependent pathway known as antibody-dependent enhancement (ADE). In this study, infection enhancement was observed when purified monocytes were infected with DV serotypes in the presence of serially diluted immune serum antibodies. Analyzing binding of the DV-antibody immune complexes to monocytes by quantifying the amount of viruses attached to monocytes, we found that binding did not correlate with the input amount of antibodies; rather, it peaked at suboptimal antibody concentrations, correlating with the observed infection enhancement. These results suggested that immune complexes are involved in hindering DV from binding to FcR-bearing cells; when such a protective feature is weakened, enhancement of viral attachment and ADE are observed. Further, increased cytokine production (TNF-alpha and IFN-alpha), and costimulatory marker expression (CD86 and CD40), were found to be associated with infection enhancement, suggesting a pathological role of ADE-affected monocytes in dengue hemorrhagic diseases.

Involvement of CD16 in antibody-dependent enhancement of porcine reproductive and respiratory syndrome virus infection

“…The bestcharacterized receptors involved in ADE of dengue virus are FccRI and FccRII (Boonnak et al, 2013;Kontny et al, 1988;Littaua et al, 1990;Mady et al, 1993). Other investigators found that FccRII is involved in ADE of infection by severe acute respiratory syndrome coronavirus, dengue virus, and coxsackievirus B (Hober et al, 2012;Kam et al, 2007;Sun et al, 2011;Yip et al, 2014). Recently, Qiao et al (2011) reported that FccRII is involved in the ADE of PRRSV infection in Marc-145 cells expressing FccRII.…”

Differential Expression of Toll-Like Receptors in Dendritic Cells of Patients with Dengue During Early and Late Acute Phases of the Disease

“…Monocytes have also been reported to represent target cells of DENV replication [48]. Moreover, Azeredo et al [31] showed an increase of TLR2 expression in monocyte CD14+ of dengueinfected patients.…”

Cytokines and Viral Hemorrhagic Fever: Potential for Therapeutic Intervention

“…If the host is infected a significant time after initial exposure with a different serotype, the subsequent disease is worse and is more likely to progress to DHF. This has been linked to antibody-dependent enhancement of infection, where pre-existing antibodies bind to the new dengue virus serotype and form an immune complex [45,46]. This immune complex associates with FcR-positive cells which increases uptake of the virus and increases several downstream immunological responses leading to more severe and potentially fatal symptoms.…”