Abstract
One of the major defense mechanisms against virus spread in vivo is the blocking of viral infectibility by neutralizing antibodies. We describe here the identification of infectious autophagy-associated dengue vesicles released from infected cells. These vesicles contain viral proteins E, NS1, prM/M, and viral RNA, as well as host lipid droplets and LC3-II, an autophagy marker. The viral RNA can be protected within the autophagic organelles since anti-dengue neutralizing antibodies do not have an effect on the vesicle-mediated transmission that is able to initiate a new round of infection in target cells. Importantly, such infectious vesicles were also detected in a patient serum. Our study suggests that autophagy machinery plays a new role in dengue virus transmission. This discovery explains the inefficiency of neutralizing antibody upon dengue infection as a potential immune evasion mechanism in vivo.
Highlights
One of the major defense mechanisms against virus spread in vivo is the blocking of viral infectibility by neutralizing antibodies
Recipient cells were seeded in the lower chamber overnight and Dengue virus (DENV)-infected donor cells were added to the apical chamber or donor cells were directly added to recipient cells, and the infection rate was analyzed by FACS at indicated times
The permeability of the membrane of transwell to DENV was verified by the infection of recipient cells resulting from the free DENV2 virions added in the upper chamber (Supplementary Fig. S1)
Summary
One of the major defense mechanisms against virus spread in vivo is the blocking of viral infectibility by neutralizing antibodies. The viral RNA can be protected within the autophagic organelles since anti-dengue neutralizing antibodies do not have an effect on the vesiclemediated transmission that is able to initiate a new round of infection in target cells. Such infectious vesicles were detected in a patient serum. Hepatitis C virus (HCV) has been reported to infect human hepatoma cell line via cell-to-cell transmission[19], eschewing from neutralizing antibodies[20] by packaging virions in exosomes[21] Despite both HCV and DENV belong to the same virus family; upregulation of exosomes has a negative effect on DENV21.
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