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Pseudorabies, also known as Aujeszky’s disease, is one of the most economically important viral diseases in pigs and is lethal to other susceptible animals (Ren et al. 2020). The causative agent, pseudorabies virus (PRV), is an enveloped virus with a large double-stranded DNA genome encoding at least 70 proteins (Wong et al. 2019). PRV belongs to the family Herpesviridae, subfamily Alphaherpesvirinae, genus Varicellovirus and infects multiple animals, such as pigs, dogs, cats, rabbits, cattle, sheep, goats, minks, foxes, wolves, lynxes, etc. (He et al. 2019; Laval and Enquist 2020). Pigs are recognized as the natural hosts for the virus, and the PRV infection causes severe neurological symptoms in piglets with almost 100% mortality, respiratory/ neurological signs in the nursery, respiratory signs in adult pigs, and reproductive disorders in sows (He et al. 2019; Ren et al. 2020). Most of the other infected non-natural animal hosts die within 24–48 h of disease onset, which is usually characterized by severe pruritus in the head and neck, accompanied by self-mutilation (Laval and Enquist 2020). Although cases of suspected PRV infections in humans have been occasionally reported in Europe, the occurrence of PRV infection in humans is still controversial owing to the lack of a definitely etiological or serological diagnosis (Wong et al. 2019). However, since 2018, several reports from China have shown that PRV could infect humans through detection of PRV nucleic acids by metagenomic next-generation sequencing (NGS) or specific antibody for PRV by ELISA (Fig. 1A, Table 1) (Zhao et al. 2018; Ai et al. 2018; Fan et al. 2020; Hu et al. 2020; Li et al. 2020; Wang et al. 2019, 2020; Yang H et al. 2019; Yang X et al. 2019; Zheng et al. 2019). Especially, Liu et al. successfully isolated a PRV strain (hSD-1/2019, GenBank no. MT468550) from a patient with acute encephalitis, providing direct evidence of PRV infection in humans (Liu et al. 2020). All 23 patients in the above study were in close contact with pigs or pork, and consisted of butchers, pork dealers, cooks, veterinarians, and swineherds (Fig. 1, Table 1). Most of these patients were either injured at work or their eyes were directly exposed to pollutants. Human-to-human transmission was not found. At the early stage of infection (usually within 7 days), a ‘‘flu-like’’ symptoms were observed, including fever (100%, 23/23), respiratory signs (72.7%, 16/22), and headache (57.9%, 11/19). Then, these symptoms rapidly progressed to neurological disorders after disease onset, including seizures/convulsions (95.7%, 22/23) and disturbance of consciousness (95.7%, 22/23). In addition, 60% (12/20) of the patients showed severe visual impairment and 77.3% (17/22) complicated by pulmonary inflammation. All patients were diagnosed with viral encephalitis, except for one patient who was diagnosed with endophthalmitis alone, probably because her eyes were directly exposed to sewage on a pig farm. Despite receiving systematic antiviral treatment, the patients had a very poor prognosis; 17.4% (4/ 23) of the patients died, 17.4% (4/23) developed blindness, and 21.7% (5/23) patients experienced severe visual impairment. In fact, at the time of writing this study, 65.2% (15/23) of the patients still had severe central nervous system symptoms such as persistent vegetative status, and memory loss, and only could follow simple instructions. A recent retrospective seroepidemiologic survey using 1335 serum samples collected from patients with encephalitis from China between 2012 and 2017 revealed that 6.52%–14.25% of the patients had specific PRV-gB antibodies (Li et al. 2020). All these evidences suggest that PRV is an emerging zoonotic pathogen that can infect humans in particular conditions, although the risk of infection remains low. Therefore, PRV should be included in the differential & Gaiping Zhang [email protected]