Human antibodies against dengue enhance dengue viral infectivity without suppressing type I interferon secretion in primary human monocytes.
It remains unclear whether antibody-dependent-enhancement (ADE) of dengue infection merely augments viral attachment and entry through Fcγ receptors or immune complex binding to Fcγ receptors triggers an intrinsic signaling cascade that changes the viral permissiveness of the cell. Using human dengue-immune sera and novel human monoclonal antibodies against dengue in combination with virologic and immunologic techniques, we found that ADE infection increased the proportion of infected primary human monocytes modestly from 0.2% ± 0.1% (no Ab) to 1.7% ± 1.6% (with Ab) but the total virus output markedly from 2 ± 2 (× 10(3)) FFU to 120 ± 153 (× 10(3))FFU. However, this increased virus production was not associated with a reduced secretion of type I interferon or an elevated secretion of anti-inflammatory cytokine, IL-10. These results demonstrate that the regulation of virus production in ADE infection of primary human monocytes is more complex than previously appreciated.
Department of Medicine, University of Rochester, Rochester, NY 14642, USA.
Zhihua
Z
Kou
Joanne Y H
JY
Lim
Martina
M
Beltramello
Matthew
M
Quinn
Huiyuan
H
Chen
Shengyong
S
Liu
Shengyo-ng
SN
Liu
Luis
L
Martinez-Sobrido
Luis
L
Martnez-Sobrido
Michael S
MS
Diamond
Jacob J
JJ
Schlesinger
Aravinda
A
de Silva
Federica
F
Sallusto
Xia
X
Jin
D000818:Animals; D000914:Antibodies, Viral / Q000502:physiology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003716:Dengue Virus / Q000276:immunology / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000502:physiology* / Q000821:virology*; D014709:Vero Cells; D053585:Virus Attachment; D053586:Virus Internalization
D000914:Antibodies, Viral; D007370:Interferon Type I; D007378:Interleukins