Human antibodies against dengue enhance dengue viral infectivity without suppressing type I interferon secretion in primary human monocytes

Zhihua Kou, Joanne Y.H. Lim, Martina Beltramello, Matthew Quinn, Huiyuan Chen, Shengyo ng Liu, Luis Martnez-Sobrido, Michael S. Diamond, Jacob J. Schlesinger, Aravinda de Silva, Federica Sallusto, Xia Jin

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43 Scopus citations

Abstract

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 (×103)FFU to 120±153 (×103)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.

Original languageEnglish
Pages (from-to)240-247
Number of pages8
JournalVirology
Volume410
Issue number1
DOIs
StatePublished - Feb 5 2011

Keywords

  • Antibody-dependent-enhancement
  • Dengue
  • Human monocyte
  • IL-10
  • Interferon

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    Kou, Z., Lim, J. Y. H., Beltramello, M., Quinn, M., Chen, H., Liu, S. N., Martnez-Sobrido, L., Diamond, M. S., Schlesinger, J. J., de Silva, A., Sallusto, F., & Jin, X. (2011). Human antibodies against dengue enhance dengue viral infectivity without suppressing type I interferon secretion in primary human monocytes. Virology, 410(1), 240-247. https://doi.org/10.1016/j.virol.2010.11.007