Molecular Determinants of Dengue Virus 2 Envelope Protein Important for Virus Entry in FcγRIIA-Mediated Antibody-Dependent Enhancement of Infection

Chotiwan, Nunya; Roehrig, John T.; Schlesinger, Jacob J.; Blair, Carol D.; Huang, Claire Y.-H.

doi:10.1016/j.virol.2014.03.031

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Molecular Determinants of Dengue Virus 2 Envelope Protein Important for Virus Entry in FcγRIIA-Mediated Antibody-Dependent Enhancement of Infection

Published Date:

Apr 18 2014

Publisher's site:

http://dx.doi.org/10.1016/j.virol.2014.03.031 New Site Icon

Source:

Virology. 0:238-246.

[PDF - 868.49 KB]

Details:

Personal Authors:

Chotiwan, Nunya ; Roehrig, John T. ; Schlesinger, Jacob J. ; Blair, Carol D. ; Huang, Claire Y.-H. ;

Keywords:

[+]

Pubmed ID:

24889243

Pubmed Central ID:

PMC4583201

Description:

Antibody-dependent enhancement (ADE) of infection may cause severe illness in patients suffering a secondary infection by a heterologous dengue virus (DENV) serotype. During ADE of infection, cross-reactive non- or poorly-neutralizing antibodies form infectious virus-Ab complexes with the newly infecting serotype and enhance virus infection by binding to the Fcγ receptors (FcγR) on FcγR-bearing cells. In this study, we determined that molecular determinants of DENV2 envelope protein critical for virus entry during non-ADE infection are also required for ADE infection mediated by FcγRIIA, and binding of virus-Ab complexes with FcγRIIA alone is not sufficient for ADE of infection. The FcγRIIA mainly plays an auxiliary role in concentrating the virus-Ab complex to the cell surface, and other primary cellular receptors are required for virus entry. Understanding the viral entry pathway in ADE of DENV infection will greatly facilitate rational designs of anti-viral therapeutics against severe dengue disease associated with ADE.

Document Type:

Journal Article

Collection(s):

CDC Public Access

Funding:

CC999999/Intramural CDC HHS/United States

Supporting Files:

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