Increased Virus Uptake Alone is Insufficient to Account for Viral Burst Size Increase during Antibody-Dependent Enhancement of Dengue Viral Infection

Abstract

Antibody-dependent enhancement (ADE) is a generally accepted hypothesis to explain increased viremia and disease severity during secondary human DENV infections. In addition to an increased number of infected cells, its mechanism has been postulated as either an increased uptake or an elevated production of viruses per infected cell during ADE infection. The latter postulate, however, has not been rigorously tested. Using Fc gamma receptor (Fcϒ R)-positive and type I IFN-positive (THP-1 and U937) or negative (K562) human myeloid cells, and a combination of techniques including flow cytometry, plaque assay, and real time qPCR assay, we found ADE infection led to significant burst size increase in all three cell types. Furthermore, we found comparable levels of virus uptake between ADE and direct dengue infection in THP-1 cells. Collectively, our results demonstrate that burst size increase is a common feature of dengue ADE infection, and that increased viral uptake during ADE infection is insufficient to account for the burst size increase. Thus, further mechanistic study is needed to uncover the intrinsic mechanisms of ADE infection.