and rapid interspecies transmission
Jinbiao Liu1,2,
Changhai Chen3, Xiangdong Li1,2
1Jiangsu Co-innovation Center for Prevention and
Control of Important Animal Infectious Diseases and Zoonoses, College of
Veterinary Medicine, Yangzhou University, Yangzhou, 225009 China.
2Joint International Research Laboratory of
Agriculture and Agri-Product Safety, the Ministry of Education of China,
Yangzhou University, Yangzhou, 225009 China.
3Jiangsu Provincial Center for Animal Disease Control
and Prevention, Nanjing, Jiangsu 210036, China.
Correspondence : Prof. Xiangdong Li, Email: 007352@yzu.edu.cn
Dear Editor,
We have some comments related to the recently published paper inTransboundary and Emerging Diseases titled “Genetic evolution
analysis of novel recombinant pseudorabies virus strain in Sichuan,
China” (Huang et al., 2020). A Chinese
pseudorabies virus (PRV) isolate named FJ62 was reported to be a natural
recombination of PRV genotype 1 from wild boar and genotype 2 from
domestic pigs. Specifically, the gB gene of PRV FJ62 shared the highest
homology (100%) with Japanese MY-1 strain from wild boar, which shared
the same nucleotide sequences with European and American PRV strains. By
contrast, gC, gD and gE genes of PRV FJ62 were closely related to
Chinese PRV variants in domestic pigs that were far removed from the
reference strains in Europe and USA.
Genetically, PRVs could be classified into two genotypes based on
genomic sequence or viral gC gene. PRV strains in China belong to
genotype 2, whereas PRV isolates from other countries belong to genotype
1. Within genotype 2, Chinese PRV isolates are further divided into two
subgenotypes: classical PRV (PRV isolates before 2011) in subgenotype 1
and PRV variants isolated since 2011 in subgenotype 2. As a large DNA
virus, the mutation and recombination rates of PRV are theoretically
slow. However, frequent inter-genotype and intra-genotype recombinations
have been reported. In a recent study, He et al (2019) reported that 29
PRVs had undergone recombination, with more inter- than intra-genotype
recombinations found. The mutation and recombination of viral
glycoproteins − such as gB, gC, gD and some other undefined protective
immunity-elicited proteins − might partially explain the incomplete
protection provided by PRV vaccine strains.
Besides frequent recombination, Chinese PRV variants undergo
preferential interspecies transmission including cows, dogs, cats,
sheep, minks, foxes, racoons, and even humans
(Wong et al., 2019,
Li et al., 2020). PRV utilizes its
glycoprotein gD to bind to cells via the nectin-1 receptor, which shares
conserved amino acid residues among different species
(Li et al., 2017). Zheng et al recently
reported a human severe pseudorabies encephalitis in Transboundary
and Emerging Diseases (Zheng et al.,
2019). Besides that, another 22 PRV variants-infected human cases have
been reported (Table 1). There are several distinct characteristics of
patients infected with PRV variants versus those infected with classical
PRV. First, humans infected with classical PRV had fever, weakness and
pruritus before progressing to neurological signs, including dysphagia
and paresthesia. The clinical signs of patients can last several months,
but all eventually recovered without any treatment. By contrast, humans
infected with PRV variants suffered severe central nervous system
disorders and fatal encephalitis. Besides encephalitis, 12 out of 23
patients also suffered from endophthalmitis, causing loss of vision. How
PRV variants invade the ocular nerve system and leads to endophthalmitis
warrants further investigation. Second, humans infected with classical
PRVs had close contact with diseased dogs, cats or cattle
(Wong et al., 2019). By contrast, all
patients infected with PRV variants had close contact with pigs. This
suggested that pigs have become the etiological source of PRV for human
infection. Third, PRV variants have been successfully isolated on cells
from cerebrospinal fluid samples of patients. Most recently, human PRV
hSD-1/2019 strain was, for the first time, isolated from cerebrospinal
fluid samples on PK-15 cells (Liu et al.,
2020). The virus was shown to be a PRV variant by next-generation
sequencing; it induced acute neurological signs in pigs, and caused high
mortality.
The above reported cases suggest that PRV could be an important
neglected occupational zoonotic pathogen in humans. Therefore, PRV
should be screened for in unexplained fever and encephalitis cases in
human, especially when patients have a history of close contact with
pigs or pig products. The mechanisms by which PRV variants lead to
encephalitis and endophthalmitis should be further explored in non-human
primate models.