HSP90α promotes fowl adenovirus serotype 4 replication in LMH cells via interacting with hexon

Heat shock protein 90 alpha (HSP90α), a conservative chaperone protein, is closely involved in signal transduction and virus proliferation, but how it engages the lifecycle of fowl adenovirus serotype 4 (FAdV-4) remains unknown. Here, we demonstrated that the expression of HSP90α was significantly upregulated in Leghorn male hepatoma (LMH) cells infected with FAdV-4. Functional study revealed that overexpression of HSP90α promoted FAdV-4 replication <i>in vitro</i>, whereas knockdown of HSP90α exerted the opposite effect. Subsequently, co-immunoprecipitation (Co-IP) assay showed that HSP90α, particularly the truncated HSP90α variant encompassing amino acid residues 286-542, interacted with hexon protein of FAdV-4. These findings collectively identify HSP90α as a critical host factor that modulates FAdV-4 replication through direct interaction with the viral hexon protein (via its 286-542 amino acid domain), thereby providing novel insights into the molecular crosstalk between FAdV-4 and host cells.