Emergence of a Pseudorabies virus variant with increased virulence to piglets
Graphical abstract
Introduction
Pseudorabies (PR) or Aujeszky’s disease (AD) caused by Pseudorabies virus (PRV), is a serious viral disease in pigs and other animals. This virus can cause nervous system disorders, respiratory disorders, reproductive failure, fever and itching, and causes huge economic losses to the swine industry in many countries (Lee and Wilson, 1979, Marcaccini et al., 2008, Mettenleiter, 1996, Pomeranz et al., 2005). PRV-infected pigs carry the virus for life in the peripheral nervous system and can infect other animals (Lee and Wilson, 1979).
Attenuated live or inactivated vaccines are widely used to control PR (Kooij, 1994, Mengeling et al., 1997, Pensaert et al., 2004, Stegeman, 1997, Visser, 1997). The Bartha-K61 strain is a safe and effective vaccine against PRV and has played an important role in the control and eradication of PR. PRV has been eradicated from domestic swine in the United States, several parts of Europe, and New Zealand (Hahn et al., 2010, Müller et al., 2011, Pannett et al., 1999). In the 1970s, the Bartha-K61 vaccine was imported from Hungary to China and used to effectively control PR (Tong and Chen, 1999). However, since late 2011, PR has occurred in Bartha-K61-vaccinated pigs on many swine farms in China (Peng et al., 2013, An et al., 2013, Wu et al., 2013, Wang et al., 2014, Yu et al., 2014, Luo et al., 2014). The symptoms of the disease were stillbirth or the birth of weak piglets with nervous system disorders, diarrhea, tremble, and opisthotonos (An et al., 2013). Since the initial outbreak in late 2011, PR has occurred in more than 15 provinces in China and has caused more than 50% mortality in infected neonatal piglets (An et al., 2013, Wang et al., 2014, Yu et al., 2014). A PRV variant was considered to be the cause of emerging PR, since the Bartha-K61 vaccine did not provide full protection against the prevalent PRV variant in sheep (An et al., 2013, Luo et al., 2014).
We isolated the PRV variant JS-2012 strain from piglets with suspected PR that had been vaccinated with Bartha-K61-vaccine (Tong et al., 2013). Phylogenetic analysis showed that JS-2012 with other emergent variants in China such as HeN1 and TJ strains formed a novel branch and relatively distant from previously isolated strains of PRV (Tong et al., 2013, Luo et al., 2014, Ye et al., 2015). Compared with Bartha strain, the emergent variants had unique insertion/deletion polymorphisms and microsatellites (Ye et al., 2015). JS-2012 strain was more pathogenic than classical virulent PRV SC strain in BALB/c mice (Tong et al., 2013). In this report, we compared the differences in pathogenicity between PRV variant JS-2012 strain and classical virulent PRV SC stain by vaccination-challenge experiment in piglets and artificial infection experiments in pigs of different age.
Section snippets
Cells and viruses
Vero cells were grown and maintained in Dulbecco’s modified Eagle’s high glucose medium (DMEM) supplemented with 10% fetal bovine serum (FBS) (Invitrogen, USA) at 37 °C in 5% CO2. The PRV SC strain isolated in China in 1980 was highly pathogenic to pigs and sheep (Yuan et al., 1987). The PRV variant JS-2012 strain was isolated from brain tissues of dead piglets in a farm in Jiangsu Province of China in which an outbreak of an emerging infectious disease characterized by newborn piglet deaths
The PRV SC- or JS-2012-specific neutralizing antibodies induced by Bartha-K61 vaccine
For the Bartha-K61-vaccinated piglets (group 1 and group 2), the PRV SC-specific NAbs titers (4.87 ± 0.36) were significantly higher than JS-2012-specific NAbs titers (2.87 ± 0.36, P < 0.01). Similarly, the PRV SC-specific NAbs titers of group 1 (4.79 ± 0.36) were significantly higher than JS-2012-specific NAbs titers of group 2 (2.92 ± 0.42, Table 1, P < 0.01). No PRV SC- or JS-2012-specific NAbs were detected in the unvaccinated control groups (group 3 and group 4, <2, Table 1).
Bartha-K61 vaccine provided complete protection against SC but not against JS-2012
In addition to a slight
Discussion
In late 2011, a PR-like infection disease characterized by a large number of newborn piglet deaths with neurologic symptoms occurred in Bartha-K61-vaccinated pigs on many farms in China (An et al., 2013, Yu et al., 2014). The PRV variants isolated in the Bartha-K61-vaccinated piglets with suspected PR were considered to be the cause of the disease (An et al., 2013, Yu et al., 2014). The Bartha-K61 vaccine did not provide complete protection against the emerging PRV variants in sheep (An et al.,
Acknowledgments
This work was supported by Shanghai Municipal Natural Science Foundation (No. 14ZR1448900), Shanghai city agriculture science and technology key project (2015,1-7), and the National Nonprofit Institute Research Grant of CATAS-ITBB (No. 2014JB02).
Wu Tong is a research associate of Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences. His research focus is on molecular epidemiology and vaccinology of Pseudorabies virus.
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