Infection and activation of human peripheral blood monocytes by dengue viruses through the mechanism of antibody-dependent enhancement.
Human monocytes are susceptible to dengue virus (DV) infection through an FcR-dependent pathway known as antibody-dependent enhancement (ADE). In this study, infection enhancement was observed when purified monocytes were infected with DV serotypes in the presence of serially diluted immune serum antibodies. Analyzing binding of the DV-antibody immune complexes to monocytes by quantifying the amount of viruses attached to monocytes, we found that binding did not correlate with the input amount of antibodies; rather, it peaked at suboptimal antibody concentrations, correlating with the observed infection enhancement. These results suggested that immune complexes are involved in hindering DV from binding to FcR-bearing cells; when such a protective feature is weakened, enhancement of viral attachment and ADE are observed. Further, increased cytokine production (TNF-alpha and IFN-alpha), and costimulatory marker expression (CD86 and CD40), were found to be associated with infection enhancement, suggesting a pathological role of ADE-affected monocytes in dengue hemorrhagic diseases.
The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. Rockville, MD 20850, USA. Peifang.sun@med.navy.mil
Peifang
P
Sun
Karolis
K
Bauza
Subhamoy
S
Pal
Zhaodong
Z
Liang
Shuenn-jue
SJ
Wu
Charmagne
C
Beckett
Timothy
T
Burgess
Kevin
K
Porter
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000378:metabolism; D000914:Antibodies, Viral / Q000276:immunology* / Q000378:metabolism; D000915:Antibody Affinity; D019067:Antibody-Dependent Enhancement; D051940:B7-2 Antigen / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D002522:Chlorocebus aethiops; D003716:Dengue Virus / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D019595:Severe Dengue / Q000276:immunology / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014709:Vero Cells; D014779:Virus Replication
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D051940:B7-2 Antigen; D019013:CD40 Antigens; D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha