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prM-reactive antibodies reveal a role for partially mature virions in dengue virus pathogenesis.
- Source :
- Proceedings of the National Academy of Sciences of the United States of America; 1/17/2023, Vol. 120 Issue 3, p1-12, 26p
- Publication Year :
- 2023
-
Abstract
- Cleavage of the flavivirus premembrane (prM) structural protein during maturation can be inefficient. The contribution of partially mature flavivirus virions that retain uncleaved prM to pathogenesis during primary infection is unknown. To investigate this question, we characterized the functional properties of newly-generated dengue virus (DENV) prM-reactive monoclonal antibodies (mAbs) in vitro and using a mouse model of DENV disease. Anti-prM mAbs neutralized DENV infection in a virion maturation state--dependent manner. Alanine scanning mutagenesis and cryoelectron microscopy of anti-prM mAbs in complex with immature DENV defined two modes of attachment to a single antigenic site. In vivo, passive transfer of intact anti-prM mAbs resulted in an antibody-dependent enhancement of disease. However, protection against DENV- induced lethality was observed when the transferred mAbs were genetically modified to inhibit their ability to interact with Fcy receptors. These data establish that in addition to mature forms of the virus, partially mature infectious prM<superscript>+</superscript> virions can also contribute to pathogenesis during primary DENV infections. [ABSTRACT FROM AUTHOR]
- Subjects :
- DENGUE viruses
VIRION
CYTOSKELETAL proteins
MONOCLONAL antibodies
IMMUNOGLOBULINS
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 120
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 161333501
- Full Text :
- https://doi.org/10.1073/pnas.2218899120