Structure of bovine viral diarrhea virus E2 glycoprotein in complex with CD46 reveals the molecular basis of virus-receptor recognition.

Authors

Yanping Duan, Sheng Lin, Fei Wang, Yu You, Zimin Chen, Liyan Guo, Wenjie Gong, Lianjing Liang, Shiyuan Tang, Hai-Fang Yu, Yarong He, Bin He, Zhi Wan, Yu Cao, Fanli Yang, Guangwen Lu

Published in

Proceedings of the National Academy of Sciences of the United States of America. Volume 123. Issue 43. Pages e2620643123. Oct 27, 2026. Epub Oct 20, 2026.

Abstract

Bovine viral diarrhea virus (BVDV) is a major contagious pathogen of ruminants and imposes substantial economic burdens on the global livestock industry. The viral envelope glycoprotein E2 mediates host cell attachment by recognizing the CD46 receptor; however, the molecular basis of this interaction remains unclear. Here, we report the crystal structure of BVDV-1 E2 in complex with bovine CD46 at 3.1-Å resolution. The structure reveals that the SCR1-2 domains of CD46 engage the DII-DIV domains of E2 in a roughly antiparallel orientation. Atomic interactions at the E2/CD46 interface are dominated by van der Waals contacts, accompanied by only a limited number of hydrogen bonds, which explains the observed low-affinity binding between the two molecules. Structural analysis and mutagenesis studies identify key receptor features that govern host susceptibility to the virus and propose an interesting bipartite model: The D'/D interloop within SCR1 of CD46 likely serves as the "molecular determinant," and key interface residues within SCR2 function as the "affinity regulator." We further engineered CD46 decoy proteins exhibiting over 1,800-fold higher apparent binding to E2 than the wild-type receptor and demonstrated their potent virus-neutralizing activity. Collectively, these findings elucidate the molecular basis of CD46 recognition by BVDV, provide a structural framework for understanding the viral host range, and establish a receptor-based strategy for potential antiviral intervention.

PMID:
42900730
Bibliographic data and abstract were imported from PubMed on 21 Oct 2026.

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