TY - JOUR
T1 - Immature Dengue Virus Is Infectious in Human Immature Dendritic Cells via Interaction with the Receptor Molecule DC-SIGN
AU - Richter, Mareike K. S.
AU - Da Silva-Voorham, Júlia M.
AU - Torres Pedraza, Silvia
AU - Hoornweg, Tabitha E.
AU - van de Pol, Denise P. I.
AU - Rodenhuis-Zybert, Izabela A.
AU - Wilschut, Jan
AU - Smit, Jolanda M.
PY - 2014/6/2
Y1 - 2014/6/2
N2 - Background: Dengue Virus (DENV) is the most common mosquito-borne viral infection worldwide. Important target cells during DENV infection are macrophages, monocytes, and immature dendritic cells (imDCs). DENV-infected cells are known to secrete a large number of partially immature and fully immature particles alongside mature virions. Fully immature DENV particles are considered non-infectious, but antibodies have been shown to rescue their infectious properties. This suggests that immature DENV particles only contribute to the viral load observed in patients with a heterologous DENV re-infection.Methodology/Principal findings: In this study, we re-evaluated the infectious properties of fully immature particles in absence and presence of anti-DENV human serum. We show that immature DENV is infectious in cells expressing DC-SIGN. Furthermore, we demonstrate that immature dendritic cells, in contrast to macrophage-like cells, do not support antibody-dependent enhancement of immature DENV.Conclusions/Significance: Our data shows that immature DENV can infect imDCs through interaction with DC-SIGN, suggesting that immature and partially immature DENV particles may contribute to dengue pathogenesis during primary infection. Furthermore, since antibodies do not further stimulate DENV infectivity on imDCs we propose that macrophages/monocytes rather than imDCs contribute to the increased viral load observed during severe heterotypic DENV re-infections.
AB - Background: Dengue Virus (DENV) is the most common mosquito-borne viral infection worldwide. Important target cells during DENV infection are macrophages, monocytes, and immature dendritic cells (imDCs). DENV-infected cells are known to secrete a large number of partially immature and fully immature particles alongside mature virions. Fully immature DENV particles are considered non-infectious, but antibodies have been shown to rescue their infectious properties. This suggests that immature DENV particles only contribute to the viral load observed in patients with a heterologous DENV re-infection.Methodology/Principal findings: In this study, we re-evaluated the infectious properties of fully immature particles in absence and presence of anti-DENV human serum. We show that immature DENV is infectious in cells expressing DC-SIGN. Furthermore, we demonstrate that immature dendritic cells, in contrast to macrophage-like cells, do not support antibody-dependent enhancement of immature DENV.Conclusions/Significance: Our data shows that immature DENV can infect imDCs through interaction with DC-SIGN, suggesting that immature and partially immature DENV particles may contribute to dengue pathogenesis during primary infection. Furthermore, since antibodies do not further stimulate DENV infectivity on imDCs we propose that macrophages/monocytes rather than imDCs contribute to the increased viral load observed during severe heterotypic DENV re-infections.
KW - WEST-NILE-VIRUS
KW - ANTIBODY-DEPENDENT ENHANCEMENT
KW - BORNE ENCEPHALITIS-VIRUS
KW - FUSION-LOOP ANTIBODY
KW - CELLULAR ATTACHMENT
KW - HEMORRHAGIC-FEVER
KW - MATURATION
KW - CLEAVAGE
KW - PRM
KW - FLAVIVIRUSES
U2 - 10.1371/journal.pone.0098785
DO - 10.1371/journal.pone.0098785
M3 - Article
C2 - 24886790
SN - 1932-6203
VL - 9
JO - PLoS ONE
JF - PLoS ONE
IS - 6
M1 - e98785
ER -