8FE3

Structure of dengue virus (DENV2) in complex with prM12, an anti-PrM monoclonal antibody

8FE3 の概要

• エントリーDOI: 10.2210/pdb8fe3/pdb
• EMDBエントリー: 29020
• 分子名称: prM12 Fab Heavy Chain, prM12 Fab Light Chain, Envelope protein E, ... (4 entities in total)
• 機能のキーワード: denv, flavivirus, prm antibody, prm12, virus-immune system complex, virus/immune system
• 由来する生物種: Mus musculus (mouse); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 303904.19

構造登録者

Dowd, A.D.,Sirohi, D.,Speer, S.,Mukherjee, S.,Govero, J.,Aleshnick, M.,Larman, B.,Sukupolvi-Petty, S.,Sevvana, M.,Miller, A.S.,Klose, T.,Zheng, A.,Kielian, M.,Kuhn, R.J.,Diamond, M.S.,Pierson, T.C. (登録日: 2022-12-05, 公開日: 2023-02-01, 最終更新日: 2024-06-19)

主引用文献

A Dowd, K.,Sirohi, D.,D Speer, S.,VanBlargan, L.A.,Chen, R.E.,Mukherjee, S.,Whitener, B.M.,Govero, J.,Aleshnick, M.,Larman, B.,Sukupolvi-Petty, S.,Sevvana, M.,Miller, A.S.,Klose, T.,Zheng, A.,Koenig, S.,Kielian, M.,Kuhn, R.J.,Diamond, M.S.,Pierson, T.C.
prM-reactive antibodies reveal a role for partially mature virions in dengue virus pathogenesis.
Proc.Natl.Acad.Sci.USA, 120:e2218899120-e2218899120, 2023

PubMed 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 Fcγ receptors. These data establish that in addition to mature forms of the virus, partially mature infectious prM virions can also contribute to pathogenesis during primary DENV infections.

PubMed: 36638211
DOI: 10.1073/pnas.2218899120

実験手法

ELECTRON MICROSCOPY (10.2 Å)