Infectivity and Potential Zoonotic Characteristics of Porcine Pseudorabies Virus in Human Cells

Pseudorabies virus (PRV) is widely spread, characterized by high contagiousness, high viral load, and strong infectivity, and poses severe threats to the global pig farming industry. Apart from pigs, PRV can also infect several other mammals, including mice, cattle, cats, dogs, and wolves, with diverse clinical symptoms. Notably, approximately more than 20 cases of human PRV infection have been reported in recent years, with fever, seizures, human encephalitis, intraocular inflammation, and severe central nervous system symptoms. However, whether PRV can infect humans or belongs to a zoonotic virus is still controversial. In this study, human neuronal cells were infected with PRV and blindly passaged to obtain human cell-adapted PRV, followed by comparing the characteristics of human cell-adapted PRV and pig-derived PRV in vitro and in vivo, to determine whether PRV has the potential to infect humans. The results showed that PRV could be stably passaged in human cells and produced progeny viruses similar to the parental virus, including morphology, infectivity, and pathogenicity. The human cell-adapted PRV can also cross-transmit to cells from other origins, including humans, mice, pigs, and monkeys, causing different cytopathic effects. Moreover, multiple tissue damage can be detected in mice infected with human cell-adapted PRV. These results demonstrate that PRV is a potential zoonotic virus, and it is necessary to pay close attention to the spread and variation of the virus in animals and humans.