Vimentin as a universal receptor for pseudorabies virus infection in pig and human cells

Pseudorabies virus (PRV), known to infect pigs and found in various species, including humans, shows zoonotic potential. This study identified vimentin (VIM), a highly conserved intermediate filament protein expressed in multiple mammalian species and tissues, as a universal receptor for PRV infections in human and porcine cells. The adsorption of PRV is positively correlated with the level of VIM expressed in different cells. Overexpression and knockdown of VIM significantly increase and decrease PRV adsorption in cells, respectively. Dot blot assay and VOPBA showed that purified VIM can directly bind to PRV virions efficiently in a dose-dependent manner. PRV and VIM are co-localized at the cell membrane of PRV-infected cells. Moreover, PRV mainly binds to host VIM via its conserved amino acid residues in PRV gD (W⁹⁸, G¹⁶², Y¹⁶⁴, C²⁰⁵) and gH (C⁴³⁹) and the Rod domain (residues 96-404) of VIM. In addition, regulating the expression of VIM also influences the entry, replication, and release of PRV, which has a similar result to the adsorption. These results demonstrate that VIM, as a universal receptor, can facilitate PRV infection in multiple stages in human and porcine cells, highlighting the zoonosis characteristics of PRV and the need for more attention.