Open AccessADAM17 is an essential attachment factor for classical swine fever virus
Author(s) -
Fei Yuan,
Dandan Li,
Changyao Li,
Yanan Zhang,
Hao Song,
Suhua Li,
Hongkui Deng,
George F. Gao,
Ai Zheng
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009393
Subject(s) - virus , classical swine fever , virology , biology , metalloproteinase , viral envelope , microbiology and biotechnology , gene silencing , matrix metalloproteinase , genetics , gene
Classical swine fever virus (CSFV) is an important pathogen in the swine industry. Virion attachment is mediated by envelope proteins E rns and E2, and E2 is indispensable. Using a pull-down assay with soluble E2 as the bait, we demonstrated that ADAM17, a disintegrin and metalloproteinase 17, is essential for CSFV entry. Loss of ADAM17 in a permissive cell line eliminated E2 binding and viral entry, but compensation with pig ADAM17 cDNA completely rescued these phenotypes. Similarly, ADAM17 silencing in primary porcine fibroblasts significantly impaired virus infection. In addition, human and mouse ADAM17 , which is highly homologous to pig ADAM17 , also mediated CSFV entry. The metalloproteinase domain of ADAM17 bound directly to E2 protein in a zinc-dependent manner. A surface exposed region within this domain was mapped and shown to be critical for CSFV entry. These findings clearly demonstrate that ADAM17 serves as an essential attachment factor for CSFV.