Anti-prM Antibody as an Autoantibody in Dengue Virus Infection

Abstract

Abstract:We have reported that anti-prM antibody is an enhancing antibody that enhances DV infection of non-Fc receptor bearing cells by dual specificity. We identified the epitope recognized by this anti-prM antibody, M3, which is located at the a.a.53-67of the prM protein nearby the prM/M cleavage junction and these anti-M3 antibodies could be detected in dengue patients sera. Surprisingly, this anti-prM antibody not only recognizes the prM protein of dengue virions, but also cross-reacts with epithelial cells, endothelial cells as well as T cells. The binding of anti-prM antibody to endothelial cells was dose-dependent and could be blocked by M3 peptides. Human M3-specific antibodies from dengue patient sera were demonstrated to be able to bind to endothelial cells and mediate ADE infection on K562 cells. Furthermore, the anti-prM antibody will mediate the antibodydependent cell phagocytosis, leading to the similar severe form of DHF/DSS. In conclusion, anti-prM antibody plays two roles in the pathogenesis of dengue virus infection: to be an enhancing antibody and an autoantibody as well.

Identification of a novel infection-enhancing epitope on dengue prM using a dengue cross-reacting monoclonal antibody

“…Consistent with prior studies [24-27,31,41,42], the mAb 4D10 and antibody against epitope peptide PL10 described in the present study showed broad cross-reactivity and poor neutralizing activity with the four standard DENV serotypes and imDENV but significantly enhanced the infectious properties. These results suggested 4D10 and anti-PL10 sera were infection-enhancing antibodies and PL10 was infection-enhancing epitope.…”

“…The epitope recognized by our own anti-prM antibody was located in amino acid residuals 14–18 of the prM protein and was different from the published sequence recognized by other anti-prM mAb 2H2 (mapped to amino acid residuals 40–49) and 70-21 (mapped to amino acid residuals 53–67) [40,41]. Previous studies have shown that 2H2 provided cross-protection against all four DENV serotypes [40,55].…”

“…Therefore, the identification of B-cell epitopes for DENV prM antibodies can provide important information for the understanding of the pathogenesis of DENV infection and contribute to the development of dengue vaccine. In the case of DENV, many efforts have been made into mapping the epitopes of E protein [35-39], but only a few epitopes have been identified on prM protein [40,41]. Consequently, the precise antigenic structures of prM and their functions in the immune response and infection pathogenesis remain poorly studied.…”

Dengue Patients Exhibit Higher Levels of PrM and E Antibodies Than Their Asymptomatic Counterparts

“…These virions are infectious and have been shown to display both mature- and immature-like patches on the same virion [ 35 ], displaying antigenic characteristics of both types [ 36 ]. Interestingly, studies have shown that antibodies against prM have been shown to enhance wild type DENV infection [ 37 ] and the levels of prM antibodies were found to be higher in patients with secondary infections compared with sera from primary DENV infections [ 38 ].…”

Dengue virus life cycle: viral and host factors modulating infectivity

“…Moreover, the presence of prM-specific antibodies in sera of DENVpositive patients suggests that immature particles are also formed during a natural infection [109,110,[185][186][187]. Incomplete cleavage of DENV has been linked to the existence of an acidic residue at position P3 within the 13-amino-acid sequence proximal to the prM cleavage site [188,189].…”