Figure 4个  Table 6
    • Target Methods Sensitivity and specificity Reference
      PRV antibody Blocking ELISA: targeting to the gB antibody High sensitivity (80.9%) and specificity (96.4%) compared with the commercial ELISA kit (IDEXX) Sun HF et al. (2018)
      Indirect ELISA: targeting to the gE antibody Total 89.1% positive coincidence rate compared with the commercial ELISA kit (IDEXX) (allowing DIVA) Zheng et al. (2017)
      Indirect ELISA: targeting to the gE antibody High 88.0% sensitivity and 91.5% specificity compared with the commercial ELISA kit (IDEXX) (allowing DIVA) Kou et al. (2018)
      Indirect ELISA: targeting to the gB antibody Highly total positive coincidence rate (97.8%) compared with the commercial ELISA kit. and the lowest detection limit was 1: 128 dilution of the positive serum Liu MM et al. (2019)
      ICA: targeting to the gE antibody The lowest detection limit was 1:1280 dilution of the positive serum, and 95.3% positive coincidence rate compared with the commercial ELISA kit (IDEXX) (allowing DIVA) Lei and Zhang (2016)
      DFM: 2 targeting to the gE antibody Total 74.7% positive coincidence rate compared with the conventional PCR, while which was more sensitive than the later one (allowing DIVA) Xu LH et al. (2017)
      Liquid chip technology: targeting to the gE antibody This method could be applied to detect both PRV and PRRSV antibodies with higher sensitivity than the commercial ELISA kits (allowing DIVA) Xiao et al. (2018)
      IFAT: targeting to the gE antibody High sensitivity (93.8%) and specificity (91.7%) compared with the commercial ELISA kit (IDEXX) (allowing DIVA) Zhu et al. (2019)
      PRV antigen LFA: targeting to the gB antigen Detection limit of inactivated PRV antigens were lower than 1 × 106.6 TCID50/0.1 mL with 86.7% positive coincidence rate compared with the conventional PCR Wang TH et al. (2018)
      PRV DNA NanoPCR: targeting to the gB, gE, and gG genes This test could be used for the differentiation of wild PRV and gene-deleted vaccine strains with higher sensitivity than the conventional PCR (allowing DIVA) Ma et al. (2013)
      DdPCR: targeting to the gE gene Higher sensitivity (6.1 copies/μL) than qPCR with high specify (96.2%) compared with viral isolation (allowing DIVA) Chen et al. (2017)
      LAMP: targeting to the gB gene Showed 100 times higher sensitivity than conventional PCR with the detection limit of 1 fg/μL Xu ZL et al. (2017)
      PCR combined with nucleic acid probe spot hybridization: targeting to the gE gene The sensitivity was 100 times higher than conventional PCR, being 10 pg/μL and 1 ng/ul, respectively (allowing DIVA) Wunaerhan et al. (2017)
      PCR: targeting to the gE, gB and TK genes This approach could be used to distinguish between PRV wild virus, SA215 and Bartha-K61 vaccine strains with detection limit of 1.8 × 106 copies/μL (allowing DIVA) Jiang et al. (2018)
      RPA: targeting to the gE and gB genes Both the sensitivities of gE and gB gene were 100 copies/μL, this approach could be used to distinguish PRV wild and attenuated virus with 100% specify compared with qPCR (allowing DIVA) Liu LB et al. (2018)
      TaqMan qPCR: targeting to the gE and gD genes The detection limits of gE and gB genes were 12.1 and 39.4 copies, respectively, which was more sensitive than qPCR and conventional PCR (allowing DIVA) Lan et al. (2018)
      QPCR: targeting to the gB gene The detection limit was lower than 1000 copies/μL, showing higher sensitivity than conventional PCR Hua et al. (2019)
      QPCR: targeting to the gE gene The detection limit was 10 copies/μl with high specificity (100%) compared with conventional PCR and commercial kits Wen et al. (2019)
      Multiple RT-PCR: targeting to the gE gene The approach could detect the nucleic acids of PRV, PCV2, PPV, PPRSV, JEV, and CSFV with the detection limit pf 10-3 ng/μL for PRV (allowing DIVA) Li et al. (2019)
      QIAxcel CGE: targeting to the gE gene This method could be applied for the detection of PRV, CSFV, JEV, PCV2, PRRSV, PPV and ASFV, with the detection limit of 4.53 × 103 copies/μL for PRV (allowing DIVA) Wu et al. (2019)
      Multiple PCR: targeting to the gE gene This method could be applied for the detection of PRV, PCV2 and PPV, with the detection limit of 72 pg/μL for PRV (allowing DIVA) Xin et al. (2019)
      NGS This approach could be used for detecting undetermined pathogens with high sensitivity Ai et al. (2018)
      DIVA: Distinction between the infected and vaccinated animals; ICA: Gold immunochromatographic assay; DFM: Direct immunofluorescence method; IFAT: Indirect immunofluorescent antibody detection method; LFA: Lateral flow assay; NanoPCR: Nanoparticle-assisted PCR assay; DdPCR: Droplet digital PCR assay; LAMP: Loop-mediated isothermal amplification; RPA: Recombinase polymerase amplification; QIAxcel CGE: QIAxcel capillary gel electrophoresis; NGS: Next generation sequencing.

      Table 1.  Various diagnostic approaches developed in China.

    • Species Case numbers Clinical signs Pathological characteristics Reference
      Cattle/cow 9 Pruritus, nervous symptoms, being excited and manic, etc Leptomeningeal hyperemia, consolidation of lung lobes, etc Cheng et al. (2019)
      Dog 12 Pruritus, hypersalivation, broken winded, etc Endocardial and thymic hemorrhage, pulmonary hemorrhage and/or congestion, etc Zhang L et al. (2015)
      Wolf 1 Pruritus, vomiting, quadriplegia, etc hemorrhagic spots and edema in the meninges Hemorrhagic spots and necrosis in the liver, etc Lian et al. (2020)
      Goat/sheep 11 Pruritus, nervous symptoms, muscle spasm, etc Leptomeningeal hyperemia, consolidation of lung lobes, etc Zhang et al. (2016)
      Fox 2 Pruritus, vomiting, broken winded, etc Sugillation in the lung, hemorrhage in the spleen, thymus and liver, etc Jin et al. (2016)
      Mink 9 Pruritus, diarrhea, muscle spasm, etc Hemorrhage in the thymus and submandibular lymph node, liver and spleen tumefaction, etc Liu et al. (2017)
      Raccoon 3 Pruritus, vomiting, etc Not mentioned Liu et al. (2016)

      Table 2.  Clinical signs and pathological characteristics of different PRV-infected species in China.

    • Date Age/Sex Occupation Injured at work Interval after injury Symptoms Diagnostic methods Treatment Reference
      NA 43/male Veterinarian Yes 4 days Fever, headache, tonic-clonic seizures and coma, etc NGS; PCR and ELISA methods Acyclovir treatment for 2 weeks; antibiotics Yang H et al. (2019)
      NA 59/male Swineherd Yes 6 days Fever, seizures, tonic-clonic seizures and coma, etc NGS, ELISA method Antimicrobial therapy, penciclovir and foscarnet sodium treatment for 17 days Zheng et al. (2019)
      NA 44/male Sick pig handler NA NA Fever, seizures, visual loss, etc NGS and PCR methods Acyclovir and other treatments Wang Y et al. (2019)
      2011 A young female NA NA Least 5 days Fever, chotic behavior, recurrent seizures, etc NGS (CSF) Acyclovir, foscarnet, VPA treatment, etc. (death) Fan et al. (2020)
      Nov 2016 42/female Pork cutter/cooker NA 4 days Fever, tonic-clonic seizures, coma, blindness, etc NA Acyclovir and other treatments Zhao et al. (2018)
      Jun 2017 46/female Swineherd Exposed to the sewage 3 days Fever, visual impairment, headaches, etc NGS, real-time PCR and PCR methods NA Ai et al. (2018)
      Dec 2017 55/male Pork cutter/cooker NA 4 days Fever, headaches, cough, coma, etc NGS (CSF) NA Zhao et al. (2018)
      Dec 2017 51/man Pork cutter/cooker NA NA Fever, headache, coma, tonic-clonic seizures and death, etc NGS (CSF) Acyclovir and other treatments Zhao et al. (2018)
      Nov 2017 38/male Pork cutter/cooker NA 4 days Fever, headache, coma, tonic-clonic seizures, etc NA Acyclovir and other treatments Zhao et al. (2018)
      2018 A mid-aged male NA NA NA Fever, bilateral retinal necrosis, consciousness loss, etc NGS (CSF) Acyclovir treatment (death) Fan et al. (2020)
      2018 A mid-aged male Pig farmer NA One month Fever, cognitive decline, consciousness loss, etc NGS (CSF) Acyclovir, foscarnet, and methylprednisolone treatment, etc Fan et al. (2020)
      2018 A young male NA NA Least 3 days Fever, seizures, consciousness loss, etc NGS (CSF) Continues renal replacement, clonazepam, VPA, acyclovir, etc Fan et al. (2020)
      Before Mar 2018 59/male Pig farmer Yes 40 days Fever, weakness, tonic-clonic seizures, respiratory failure, etc NGS (CSF) Penciclovir treatment combined with Sodium phosphonate Fan et al. (2018)
      Feb 2018 50/male Pig slaughterer Yes 5 days Fever, headache, visual disturbance, coma, etc NGS IVIG treatment for 5 days, Glucocorticoids, antiviral and other treatments Yang X et al. (2019)
      Mar 2018 50/female Pork cutter Yes 7 days Fever, coma, respiratory failure, seizure, etc NGS Yang X et al. (2019)
      Mar 2018 43/male Sick pig handler Yes 7 days Fever, extremity tremors, respiratory failure, etc NGS Yang X et al. (2019)
      Apr 2018 59/male Pork cutter Yes 10 days Fever, seizures, respiratory failure, etc NGS Yang X et al. (2019)
      Apr 2018 50/male Pork cutter NA NA Fever, seizure, respiratory failure, etc NGS Yang X et al. (2019)
      Apr 2018 25/male Veterinarian Exposed to the PRV infected pigs 6 days Fever, headache, cognitive impairment, seizures, consciousness loss, and meningeal irritation sign NGS (CSF), DdPCR, etc Ganciclovir and foscarnet treatment Liu Q et al. (2020)
      Aug 2018 43/male Veterinarian Exposed to the diseased pigs 11 days Fever, respiratory failure, headache, cognitive impairment, seizures, consciousness loss, and meningeal irritation sign Virus isolation, NGS (CSF), ddPCR, etc Acyclovir treatment Liu Q et al. (2020)
      Mar 2019 44/male Pork cutter Yes 14 days Fever, seizure, tonic-clonic seizures and coma, etc NGS and PCR methods Acyclovir, dexamethasone and other treatments Wang et al. (2020)
      Mar 2019 35/male Pig butcher Exposed to the pigs and pork 7 days Fever, respiratory failure, headache, cognitive impairment, seizures, and consciousness loss NGS (CSF), ddPCR, etc Acyclovir and foscarnet treatment Liu Q et al. (2020)
      Feb 2019 49/male Pig butcher Exposed to the pork 3 days Fever, respiratory failure, headache, cognitive impairment, seizures, and consciousness loss NGS (CSF), ddPCR, etc Ganciclovir and foscarnet treatment Liu Q et al. (2020)
      NA: no available; NGS: next generation sequencing; CSF: cerebral spinal fluid; DdPCR: droplet digital PCR.

      Table 3.  Human PRV infection cases in China.

    • Gene-deleted vaccines Strain Features Technologies Main advantages Status References
      Single gene-deleted vaccine (inactivated) AH02LA (variant) gE-deleted BCA High safe without virulence reversion; Allowing DIVA with more complete protection than Bartha K61 vaccines Not available Wang J et al. (2016)
      HN1201 (variant) gE-deleted HR Licensed Wang T et al. (2015)
      Double gene-deleted vaccine (inactivated) ZJ01 (variant) gE/gI-deleted BCA Not available Gu et al. (2015)
      Single gene-deleted vaccine TJ (variant) gE-deleted HR Safe to piglets without visible gross pathological lesions; Effective immune response; Completely provides protection against emerging PRV variants; Allowing DIVA; Not available Wang et al. (2014)
      Double gene-deleted vaccine Ea (classical) TK/gG deleted NA Licensed He et al. (2006)
      JS-2012 (variant) gE/gI-deleted HR Not available Tong et al. (2016)
      XJ (variant) Yin et al. (2017)
      AH02LA (variant) TK/gE deleted HR Not available Wang J et al. (2018)
      JS-2012 (variant) gE/US2 deleted High-temperature passage Not available Liang et al. (2017)
      Triple gene-deleted vaccine Fa (classical) gE/gI/TK-deleted HR Safer than double gene-deleted vaccines to piglets and growing pigs; Effective immune response; Completely provides protection against emerging PRV variants; Allowing DIVA; Licensed Zhu et al. (2004)
      SA215 (classical)
      ZJ01 (variant) Not available Dong et al. (2017)
      SMX (variant) Not available Hu RM et al. (2015)
      HN1201 (variant) Not available Zhang C et al. (2015)
      HeN1 (variant) gE/gI/TK-deleted CRISPR/Cas9 Not available Tang et al. (2016)
      NY (variant) Not available Zhao et al. (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.

      Table 4.  List of genetic modified vaccines against PRV infection.

    • Insertion sites in PRV genome Parental PRV strains Insertion genes Function (animal model) References
      gG gene HB-98 strain Porcine IL6 gene and VP2 gene of PPV Provided partial protection against the virulent PPV and PRV challenges (mice) Zheng et al. (2020)
      gI gene gE/gI/TK-deleted SA 215 strain VP2 gene of PPV Completely protected pigs against maternal PRV infection and significantly reduced the death rate (1/28) after PPV challenge compared with the control (7/31) (pig) Chen et al. (2011)
      gG gene HB-98 strain Porcine IL18 gene and Cap gene of PCV2 Protected mice against PRV variants infection and significantly reduced the amount of PCV2 viremia (mice) Zheng et al. (2015)
      Between gE and gI gene gE/TK-deleted strain prM and E genes of JEV Provided 100% and 80% protection against PRV and JEV infection, respectively (mice) Qian et al. (2015)
      Between gE and gI gene gE/gI-deleted strain E2 gene of CSFV Provided complete protection against maternal PRV and CSFV infection (pig) Wang YM et al. (2015)
      gE/gI/TK-deleted TJ strain Lei JL et al. (2016)
      Between gG and gD gene gE/gI-deleted JS-2012 strain Provided complete protection against maternal PRV and CSFV infection without MDAs (pig) Tong W et al. (2020)
      Between gG and US9 gene gE/gI/TK-deleted TJ strain Cap gene of PCV2 and E2 gene of CSFV Only protected pigs against PRV infection (pig) Abid et al. (2019)
      gG gene gG deleted strain SiRNA targeting to the N gene of HP-PRRSV Safe to pigs and efficiently inhibited HP-PRRSV replication in vivo (pig) Cao et al. (2015)
      Between gE and gI gene gE/TK-deleted strain Bp26 gene of Brucella melitensis Induced good humoral and cell-mediated immune response in mice (mice) Yao et al. (2015)
      gG gene HB-98 strain SAG1 and MIC genes of Toxoplasma gondii Induced partial protection against a lethal challenge with Toxoplasma gondii strain (mice) Nie et al. (2011)
      Between gE and gI gene gE/gI/TK-deleted TJ strain P12A and 3C genes of FMDV Significantly increased the survival rate (3/5) after FMDV challenge compared with the control (0/5) (pig) Zhang et al. (2011)
      PPV: porcine parvovirus; PCV2: porcine circovirus type 2; JEV: Japanese encephalitis virus; CSFV: classical swine fever virus; HP-PRRSV: high pathogenic porcine reproductive and respiratory syndrome virus.

      Table 5.  List of live attenuated recombinant vaccines against PRV infection.

    • Source Extracts Mechanism IC50 CC50 In vitro In vivo PRV strain MOI References
      Resveratrol Ethanol Inhibition of viral replication; Inhibition of IKB kinase activation > 262.87 μmol/L 17.17 ± 0.35 μmol/L Rong A 0.01 Chen et al. (2019), Zhao et al. (2017)
      Germacrone Dimethyl sulfoxide Inhibition of viral replication 233.5 μmol/L for Vero, 184.1 μmol/L for PK15 54.51 μmol/L for Vero, 88.78 mol/L for PK15 × PRV variant Bartha K61 vaccine 0.1-10 He et al. (2019b)
      Isatis indigotica (leaf) Ethanol Inhibition of viral replication 226 μg/mL 11 μg/mL × TNL 100 pfu/well Hsuan et al. (2009)
      Radix isatidis Ethanol and water Inhibition of viral replication; Killing virus directly Not mentioned Not mentioned × MinA 100 TCID50 Tong C et al. (2020)
      Marine Bacillus S-12-86 lysozyme Water Inhibition of viral replication 100 μg/mL 0.46 μg/mL × Attenuated Not mentioned Zhu et al. (2013)
      Diammonium glycyrrhizin Not mentioned Killing virus directly 1.25 mg/mL Not mentioned Bartha K61 vaccine 104 pfu/mL Sui et al. (2010)
      Vanadium-substituted Heteropolytungstate DMEM Killing virus directly 400 μg/mL 5 μg/mL × Bartha 200 TCID50/mL Liu et al. (1998)
      Graphene Oxide DMEM Killing virus directly Not mentioned Not mentioned × HNX variant 0.01 Ye S et al. (2015)
      Ivermectin Dimethyl sulfoxide Blocking the nuclear translocation of viral DNA polymerase UL42 Not mentioned Not mentioned Not mentioned 0.01 Lv et al. (2018)
      Phosphonoformate sodium Not mentioned Inhibition of viral DNA polymerase 480 μg/mL Nearly 60 μg/mL × Kaplan 2 Ren et al. (2011)

      Table 6.  Different types of compounds with anti-PRV infection activity.