Pseudorabies virus (PRV) strain with defects in gE, gC, and TK genes protects          piglets against an emerging PRV variant

Lin, Jie; Li, Zhaolong; Feng, Zhenqing; Fang, Zhou; Chen, Jianghua; Chen, Wengzhi; Liang, Wangwang; Chen, Qi

doi:10.1292/jvms.20-0176

Cited by 20 publications

(17 citation statements)

References 22 publications

(26 reference statements)

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“…We tested 3 kinds of antibodies, i.e., p54, pI226R, and the neutralization-like antibody. p54 antibody production conformed to the regular pattern of humoral immune responses of the other attenuated ASFVs ( 23 , 28 ) and other kinds of viral vaccines ( 29 ). The antibody level was detectable at day 9 after inoculation, peaked at around 15 to 17 days postinoculation, and was maintained until the end of the experiment.…”

Section: Resultsmentioning

confidence: 56%

African Swine Fever Virus Bearing an I226R Gene Deletion Elicits Robust Immunity in Pigs to African Swine Fever

Zhang

et al. 2021

J Virol

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African swine fever (ASF) is a severe hemorrhagic infectious disease in pigs caused by the African swine fever virus (ASFV), leading to devastating economic losses in the epidemic regions. Its control currently depends on thorough culling and clearance of the diseased and the surrounding suspected pigs. ASF vaccine has been extensively explored for years worldwide, especially in hog-intensive areas where it is highly desired, but it is still unavailable due to numerous reasons. Herein, we reported another ASF vaccine candidate named SY18ΔI226R bearing a deletion of the I226R gene in replacement of an eGFP expression cassette at the right end of the viral genome. This deletion results in complete loss of virulence of SY18 as the gene-deleted strain does not cause any clinical symptoms in all pigs inoculated with either a dosage of 10 4.0 TCID 50 or 10 7.0 TCID 50 . An apparent viremia with the gradual decline was monitored, while the virus shedding was only occasionally detected in oral- or anal swabs. ASFV specific antibody appeared at 9 days post-inoculation. After intramuscular challenge with its parental strain ASFV SY18 on 21 days post inoculation, all the challenged pigs survived without obvious febrile or abnormal clinical signs. No viral DNA could be detected on the dissection of any tissue when viremia disappeared. These indicated that SY18ΔI226R is safe in swine and elicits a robust immunity to the virulent ASFV infection. IMPORTANCE: Outbreaks of African swine fever have resulted in devastating losses to the swine industry worldwide, but there is currently no commercial vaccine available. Although several vaccine candidates have been reported, none has been approved for use due to several reasons, especially the ones concerning bio-safety. Here, we identified a new undescribed functional gene, I226R. When deleted from the ASFV genome, the virus completely loses its virulence in the swine. Importantly, pigs infected with this gene-deleted virus were resistant to infection by an intramuscular challenge of 10 2.5 or 10 4.0 TCID 50 of its virulent parental virus. Furthermore, rarely the nucleic acid of the gene-deleted virus and its virulent parental virus was detected from oral- or anal swabs. Viruses could not be detected in any tissues after necropsy when viremia became negative, indicating that robust immunity was achieved. Therefore, SY18ΔI226R is a novel, ideal and efficacious vaccine candidate for genotype II ASF.

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Section: Resultsmentioning

confidence: 56%

African Swine Fever Virus Bearing an I226R Gene Deletion Elicits Robust Immunity in Pigs to African Swine Fever

Zhang

et al. 2021

J Virol

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“…( 2020 ) 201,715 (variant) gE/gC/TK -deleted CRISPR/Cas9 Not available Lin et al . ( 2020 ) Four gene-deleted vaccine C (variant) gI/gE/Us9/Us2 -deleted Natural losses Licensed Gao et al . ( 2015 ) HR: homologous DNA recombination; DIVA: distinction between the infected and vaccinated animals; BCA: bacterial artificial chromosome; CRISPR/Cas9: clustered regularly interspaced short palindromic repeats/Cas9.…”

Section: Main Vaccines Against Prv Infectionmentioning

confidence: 99%

Current Status and Challenge of Pseudorabies Virus Infection in China

et al. 2021

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Pseudorabies (PR), also called Aujeszky’s disease, is a highly infectious disease caused by pseudorabies virus (PRV). Without specific host tropism, PRV can infect a wide variety of mammals, including pig, sheep, cattle, etc., thereby causing severe clinical symptoms and acute death. PRV was firstly reported in China in 1950s, while outbreaks of emerging PRV variants have been documented in partial regions since 2011, leading to significant economic losses in swine industry. Although scientists have been devoting to the design of diagnostic approaches and the development of vaccines during the past years, PR remains a vital infectious disease widely prevalent in Chinese pig industry. Especially, its potential threat to human health has also attracted the worldwide attention. In this review, we will provide a summary of current understanding of PRV in China, mainly focusing on PRV history, the existing diagnosis methods, PRV prevalence in pig population and other susceptible mammals, molecular characteristics, and the available vaccines against its infection. Additionally, promising agents including traditional Chinese herbal medicines and novel inhibitors that may be employed to treat this viral infection, are also discussed.

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“…In addition to concern about the control of PRV infection, PRV has been used as a model organism to study the molecular biology of herpesviruses [ 5 ]. The PRV-infected pigs exhibit a variety of clinical symptoms, including high mortality in piglets, growth retardation in adult pigs, and reproductive failure in sows, which causes substantial economic losses to swine industry [ 6 ]. PRV usually induces latent-infection in adult pigs, and the hosts behave normally and show no clinical symptoms [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

The antiviral activity of kaempferol against pseudorabies virus in mice

Wang

et al. 2021

BMC Vet Res

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Background Pseudorabies virus (PRV), a member of the Alphaherpesviruses, is one of the most important pathogens that harm the global pig industry. Accumulated evidence indicated that PRV could infect humans under certain circumstances, inducing severe clinical symptoms such as acute human encephalitis. Currently, there are no antiviral drugs to treat PRV infections, and vaccines available only for swine could not provide full protection. Thus, new control measures are urgently needed. Results In the present study, kaempferol exhibited anti-PRV activity in mice through improving survival rate by 22.22 %, which was higher than acyclovir (Positive control) with the survival rate of 16.67 % at 6 days post infection (dpi); meanwhile, the survival rate was 0 % at 6 dpi in the infected-untreated group. Kaempferol could inhibit the virus replication in the brain, lung, kidney, heart and spleen, especially the viral gene copies were reduced by over 700-fold in the brain, which was further confirmed by immunohistochemical examination. The pathogenic changes induced by PRV infection in these organs were also alleviated. The transcription of the only immediate-early gene IE180 in the brain was significantly inhibited by kaempferol, leading to the decreased transcriptional levels of the early genes (EPO and TK). The expression of latency-associated transcript (LAT) was also inhibited in the brain, which suggested that kaempferol could inhibit PRV latency. Kaempferol-treatment could induce higher levels of IL-1β, IL-4, IL-6, TNF-α and IFN-γ in the serum at 3 dpi which were then declined to normal levels at 5 dpi. Conclusions These results suggested that kaempferol was expected to be a new alternative control measure for PRV infection.

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Pseudorabies virus (PRV) strain with defects in gE, gC, and TK genes protects piglets against an emerging PRV variant

Cited by 20 publications

References 22 publications

African Swine Fever Virus Bearing an I226R Gene Deletion Elicits Robust Immunity in Pigs to African Swine Fever

African Swine Fever Virus Bearing an I226R Gene Deletion Elicits Robust Immunity in Pigs to African Swine Fever

Current Status and Challenge of Pseudorabies Virus Infection in China

The antiviral activity of kaempferol against pseudorabies virus in mice

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