Human infection with pseudorabies virus: review of evidence, risk assessment, and future directions

Pseudorabies virus (PRV) is an alphaherpesvirus with a broad host range, with the pig as its natural host. Although PRV can use human cell surface receptors for cell entry, humans and higher primates have been considered as refractory or showing very limited susceptibility to PRV infection. Between 1914 and 2011, only 17 cases of suspected human PRV infection were described, typically displaying temporal and mild/intermediate disease symptoms, mostly consisting of severe itching. No neurological complications were reported. In addition, in 1970, one researcher conducted a repetitive PRV self-inoculation experiment, which resulted in neither symptoms nor seroconversion. However, since 2011 and mostly based on next-generation sequencing on cerebrospinal fluid, 34 human cases of suspected PRV infection have been reported, all of which were linked with severe, life-threatening encephalitis and/or visual impairment. All these cases were reported in China, where there has been a concomitant surge in outbreaks of PRV strains that show genetic differences compared to classical PRV strains. All suspected recent cases of human PRV infection had (occupational) contact with raw pig meat and often had skin damage on the hands or fingers, or direct eye contact with potentially PRV-infected material. Importantly, human-to-human PRV infection has never been reported. Although the risk for human PRV infection remains very low, these recent developments should guide increased efforts to eradicate PRV from domestic pig populations, increase protection of individuals at risk, and increase research on improved diagnostics, effective antivirals, and a better understanding of the host and viral factors that determine human susceptibility or resistance to PRV infection.