A high-temperature passaging attenuated Pseudorabies vaccine protects piglets completely against emerging PRV variant

Liang, Chao; Wu, Tong; Zheng, Hao; Liu, Fei; Wu, Jiqiang; Li, Guoxin; Zhou, En‐Min; Tong, Guangzhi

doi:10.1016/j.rvsc.2017.02.008

Cited by 13 publications

(7 citation statements)

References 26 publications

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“…In our previous study, the PRV JS-2012 strain was serially passaged at high temperature for 120 generations. As the passage number increased, viruses showed a progressive attenuation in the piglet infection model, up to the point of completely losing its ability to cause death in piglets by passage 120 [16]. To characterize the evolution and variation of the viral population during passaging, in this study, several representative strains at various steps of the serial passage were characterized in vitro and in vivo, and the genome of F50, F91, and F120 was sequenced and further analyzed.…”

Section: Discussionmentioning

confidence: 99%

“…In our previous work we developed an attenuated PRV by serial passage of the variant JS-2012 in Vero cells at 40 °C for 120 generations [16]. Pathogenicity in piglets of the resulting strains F50, F91, and F120 (named according to passage number) showed that pathogenicity gradually declined as the number of passages increased, with JS-2012-F120 being avirulent in 2-week-old piglets [16]. But the relationship between virus attenuation and genetic variation during the process of serial passaging is still not clear.…”

Section: Introductionmentioning

confidence: 99%

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Comparative genomic analyses of a virulent pseudorabies virus and a series of its in vitro passaged strains

et al. 2018

Virol J

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BackgroundPseudorabies virus (PRV) of the family Herpesviridae is the causative agent of Aujeszky’s disease. Attenuation of PRV by serial passaging in vitro is a well-established method; however, the dynamic variations occurring on viral genome during this process have not been characterized.MethodsGenome sequencing and comparative genomic analyses of a virulent pseudorabies virus and a series of its plaque-purified strains via serial passaging in vitro were performed, and the properties in vitro and in vivo of which were further characterized.ResultsCompared to the parental virus, replication in vitro was enhanced in the highly passaged F50, F91, and F120. In contrast, lethality in mice decreased gradually with passage number. Genome sequencing of F50, F91, and F120 showed deletion of a large fragment containing gE, which is likely related to their attenuation. In addition, single nucleotide variations were identified in many genes of F50, F91, and F120. In-frame and frameshift indels were also detected in specific genes of passaged strains. Particularly frameshift mutations were observed in highly passaged strains, resulting in a truncated but overexpressed pUL46.ConclusionDuring attenuation of PRV by serial passaging in Vero cells, dynamic variation patterns including a large deletion, single nucleotide variations, small in-frame indels, and also frameshifts mutations successively emerged, contributing to evolution of the viral population and enabling the gradual attenuation of the virus. These data provide clues to better understand PRV attenuation during passaging.Electronic supplementary materialThe online version of this article (10.1186/s12985-018-1102-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparative genomic analyses of a virulent pseudorabies virus and a series of its in vitro passaged strains

et al. 2018

Virol J

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“…Pseudorabies virus (PRV; also called Aujeszky's disease or Suid herpesvirus type 1), which belongs to the Alphaherpesvirinae subfamily and genus Varicellovirus in the family Herpesviridae, causes fatal encephalitis in newborn piglets, respiratory disorders in growing-fattening pigs, and reproductive failure in sows. In the past, PRV was thought to not infect humans and just infect mammals including pigs, cattle, sheep, goats, dogs, cats, foxes, rats, and wild mice (1). Recently, Ai et al reported a case of human endophthalmitis caused by PRV infection (2), which suggested that it was possible for PRV to infect humans.…”

Section: Introductionmentioning

confidence: 99%

A Case of Human Viral Encephalitis Caused by Pseudorabies Virus Infection in China

et al. 2019

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We report a human case of viral encephalitis caused by pseudorabies virus (PRV) in China. A 43-year-old man with no previous medical history presented with high-grade fever, headache and tonic-clonic seizures as well as coma. Plain computer tomography (CT) brain imaging showed hypo-density in the bilateral basal ganglia, bilateral occipital lobe, bilateral limbic lobe, and left thalamic. Next-generation sequencing (NGS) confirmed the presence of PRV in cerebral spinal fluid (CSF). Regular polymerase chain reaction (PCR) was applied to confirm the presence of PRV in the CSF and blood. In addition, serological (immunological) tests were used to further validate the presence of PRV in the peripheral blood. This case suggested that it was possible for PRV to result in human central nervous system (CNS) infection, and it is necessary for people to increase awareness of self-protection when contacting animals.

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“…In herpes simplex virus, gI and gE null mutants lead to the formation of small plaques (34), and in PRV, the deletion of gI/gE/TK/UL13 also resulted in the formation of small plaques (35), which was consistent with the findings in our study. An attenuated PRV strain with the deletion of US8/11k/28k genes results in a higher titer and larger plaque size than that of WT treatment in Vero cells (36), while the larger size of the plaque formed by JS-2012 was considered induced by the cell adaption in Vero cells (120 passages).…”

Section: Discussionmentioning

confidence: 99%

Construction and Immunogenicity of a Recombinant Pseudorabies Virus Variant With TK/gI/gE/11k/28k Deletion

Yan¹,

Huang²,

Bai³

et al. 2022

Front. Vet. Sci.

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In China, the re-emerging pseudorabies virus (PRV) variant has caused large-scale outbreaks of pseudorabies in swine herds with classical PRV vaccine immunization since late 2011. Here, a recombinant PRV with TK/gI/gE/11k/28k deletion was constructed based on variant HN1201 strain isolated in 2012, by the bacterial artificial chromosome infectious clones. Compared with the parental virus, the recombinant PRV rHN1201TK−/gE−/gI−/11k−/28k− showed a similar virus grown curve and exhibited smaller plaques. The vaccination of rHN1201TK−/gE−/gI−/11k−/28k− could elicit an earlier and higher level of gB antibody, and the neutralizing antibodies elicited by rHN1201TK−/gE−/gI−/11k−/28k− were effective against both PRV classical and variant strains. Clinically, the body temperature of the pigs immunized with rHN1201TK−/gE−/gI−/11k−/28k− was significantly lower than that of the classical PRV vaccine immunized pigs, and the recombinant PRV could provide effective protection against the challenge with the PRV variant. These results imply that the rHN1201TK−/gE−/gI−/11k−/28k− could be a promising vaccine candidate for the prevention of the current epidemic of pseudorabies in China.

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A high-temperature passaging attenuated Pseudorabies vaccine protects piglets completely against emerging PRV variant

Cited by 13 publications

References 26 publications

Comparative genomic analyses of a virulent pseudorabies virus and a series of its in vitro passaged strains

Comparative genomic analyses of a virulent pseudorabies virus and a series of its in vitro passaged strains

A Case of Human Viral Encephalitis Caused by Pseudorabies Virus Infection in China

Construction and Immunogenicity of a Recombinant Pseudorabies Virus Variant With TK/gI/gE/11k/28k Deletion

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