• An, T.Q., Peng, J.M., Tian, Z.J., Zhao, H.Y., Li, N., Liu, Y.M., Chen, J.Z., Leng, C.L., Sun, Y., Chang, D., Tong, G.Z., 2013. Pseudorabies virus variant in Bartha-K61-vaccinated pigs, China, 2012. Emerg Infect Dis 19, 1749–1755.

  • Ashburner, M., Ball, C.A., Blake, J.A., Botstein, D., Butler, H., Cherry, J.M., Davis, A.P., Dolinski, K., Dwight, S.S., Eppig, J.T., 2000. Gene ontology: tool for the unification of biology. Nat. Genet. 25, 25.

  • Beausoleil, S.A., Villén, J., Gerber, S.A., Rush, J., Gygi, S.P., 2006. A probability-based approach for high-throughput protein phosphorylation analysis and site localization.Nature biotechnology 24, 1285.

  • Beck, F., Geiger, J., Gambaryan, S., Solari, F.A., Dell'Aica, M., Loroch, S., Mattheij, N.J., Mindukshev, I., Pötz, O., Jurk, K., Burkhart, J.M., Fufezan, C., Heemskerk, J.W., Walter, U., Zahedi, R.P., Sickmann, A., 2017. Temporal quantitative phosphoproteomics of ADP stimulation reveals novel central nodes in platelet activation and inhibition. Blood 129, e1–e12.

  • Bhoumik, A., Ronai, Z., 2008. ATF2-A transcription factor that elicits oncogenic or tumor suppressor activities. Cell Cycle 7, 2341–2345.

  • Duzgun, S.A., Yerlikaya, A., Zeren, S., Bayhan, Z., Okur, E., Boyaci, I., 2017. Differential effects of p38 MAP kinase inhibitors SB203580 and SB202190 on growth and migration of human MDA-MB-231 cancer cell line. Cytotechnology 69, 711–724.

  • Flori, L., Rogel-Gaillard, C., Cochet, M., Lemonnier, G., Hugot, K., Chardon, P., Robin, S., Lefevre, F., 2008. Transcriptomic analysis of the dialogue between Pseudorabies virus and porcine epithelial cells during infection. BMC Genom. 9, 123.

  • Freuling, C.M., Muller, T.F., Mettenleiter, T.C., 2017. Vaccines against pseudorabies virus(PrV). Vet. Microbiol. 206, 3–9.

  • Gueorguiev, V.D., Cheng, S.Y., Sabban, E.L., 2006. Prolonged activation of cAMPresponse element-binding protein and ATF-2 needed for nicotine-triggered elevation of tyrosine hydroxylase gene transcription in PC12 cells. J. Biol. Chem. 281, 10188–10195.

  • Gupta, S., Campbell, D., Derijard, B., Davis, R.J., 1995. Transcription factor ATF2 regulation by the JNK signal transduction pathway. Science 267, 389–393.

  • Hai, T.W., Liu, F., Coukos, W.J., Green, M.R., 1989. Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNAbinding heterodimers. Genes Dev. 3, 2083–2090.

  • He, F., Xiao, Z., Yao, H., Li, S., Feng, M., Wang, W., Liu, Z., Wu, J., 2019. The protective role of microrna-21 against coxsackievirus b3 infection through targeting the map2k3/p38 mapk signaling pathway. J. Transl. Med. 17, 335.

  • Inoue, S., Mizushima, T., Ide, H., Jiang, G., Goto, T., Nagata, Y., Netto, G.J., Miyamoto, H., 2018. ATF2 promotes urothelial cancer outgrowth via cooperation with androgen receptor signaling. Endocr. Connect 7, 1397–1408.

  • Kanehisa, M., Goto, S., 2000. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28, 27–30.

  • Kumar, A., Manna, S.K., Dhawan, S., Aggarwal, B.B., 1998. HIV-tat protein activates c-Jun N-terminal kinase and activator protein-1. J. Immunol. 161, 776–781.

  • Larsen, M.R., Thingholm, T.E., Jensen, O.N., Roepstorff, P., Jørgensen, T.J.D., 2005. Highly selective enrichment of phosphorylated peptides from peptide mixtures using Titanium dioxide microcolumns. Mol. Cell. Proteomics 4, 873–886.

  • Li, A., Lu,G., Qi,J., Wu, L., Tian, K.,Luo, T., Shi, Y., Yan, J., Gao, G.F., 2017. Structural basis of nectin-1 recognition by pseudorabies virus glycoprotein D. PLoS Pathog. 13, e1006314.

  • Lim, J.Y., Park, S.J., Hwang, H.Y., Park, E.J., Nam, J.H., Kim, J., Park, S.I., 2005. TGF-beta 1 induces cardiac hypertrophic responses via PKC-dependent ATF-2 activation. J. Mol. Cell. Cardiol. 39, 627–636.

  • Liu, F., Zheng, H., Tong, W., Li, G.X., Tian, Q., Liang, C., Li, L.W., Zheng, X.C., Tong, G.Z., 2016. Identification and analysis of novel viral and host dysregulated micrornas in variant pseudorabies virus-infected pk15 cells. PLoS One 11, e0151546.

  • Ma, J., Chang, K., Peng, J., Shi, Q., Gan, H., Gao, K., Feng, K., Xu, F., Zhang, H., Dai, B., Zhu, Y., Shi, G., Shen, Y., Zhu, Y., Qin, X., Li, Y., Zhang, P., Ye, D., Wang, C., 2018. Spop promotes atf2 ubiquitination and degradation to suppress prostate cancer progression. J. Exp. Clin. Cancer Res. 37, 145.

  • Macek, B., Mann, M., Olsen, J.V., 2009. Global and site-specific quantitative phosphoproteomics: principles and applications. Annu. Rev. Pharmacol. Toxicol. 49, 199–221.

  • McLean, T., Bachenheimer, S., 1999. Activation of cjun n-terminal kinase by herpes simplex virus type 1 enhances viral replication. J. Virol. 73, 8415–8426.

  • Mettenleiter, T.C., 2000. Aujeszky's disease (pseudorabies) virus: the virus and molecular pathogenesis-state of the art. Vet. Res. 31, 99–115.

  • Mosmann, T., 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65, 55–63.

  • Moynagh, J., 1997. Aujeszky's disease and the European Community. Vet. Microbiol. 55, 159–166.

  • Murata, T., Noda, C., Saito, S., Kawashima, D., Sugimoto, A., Isomura, H., Kanda, T., Yokoyama, K.K., Tsurumi, T., 2011. Involvement of jun dimerization protein 2 (jdp2) in the maintenance of epstein-barr virus latency. J. Bio. Chem. 286, 22007–22016.

  • Olsen, J.V., Blagoev, B., Gnad, F., Macek, B., Kumar, C., Mortensen, P., Mann, M., 2006. Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 127, 635–648.

  • Ouwens, D.M., de Ruiter, N.D., van der Zon, G.C., Carter, A.P., Schouten, J., van der Burgt, C., Kooistra, K., Bos, J.L., Maassen, J.A., van Dam, H., 2002. Growth factors can activate ATF2 via a two-step mechanism: phosphorylation of Thr71 through the Ras-MEK-ERK pathway and of Thr69 through RalGDS-Src-p38. Embo J. 21, 3782–3793.

  • Pensaert, M., Morrison, R., 2000. Challenges of the final stages of the adv eradication program. Vet. Res. 31, 141–145.

  • Ravikumar, V., Jers, C., Mijakovic, I., 2015. Elucidating host-pathogen interactions based on post-translational mmodifications using proteomics aapproaches. Front. Microbiol. 6, 1313.

  • Söderholm, S., Kainov, D.E., Öhman, T., Denisova, O.V., Schepens, B., Kulesskiy, E., Imanishi, S.Y., Corthals, G., Hintsanen, P., Aittokallio, T., 2016. Phosphoproteomics to characterize host response during influenza A virus infection of human macrophages. Mol. Cell. Proteomics 15, 3203–3219.

  • Recio, J.A., Merlino, G., 2002. Hepatocyte growth factor/scatter factor activates proliferation in melanoma cells through p38 MAPK, ATF-2 and cyclin D1. Oncogene 21, 1000–1008.

  • Rodems, S.M., Spector, D.H., 1998. Extracellular signal-regulated kinase activity is sustained early during human cytomegalovirus infection. J. Virol. 72, 9173–9180.

  • Salinas-Abarca, A.B., Velazquez-Lagunas, I., Franco-Enzástiga, Ú., Torres-López, J.E., Rocha-González, H.I., Granados-Soto, V., 2018. ATF2, but not ATF3, participates in the maintenance of nerve injury-induced tactile allodynia and thermal hyperalgesia. Mol. Pain 9, 12.

  • Schagger, H., 2006. Tricine-SDS-PAGE. Nat. Protocols 1, 16–22.

  • Sharma-Walia, N., Krishnan, H.H., Naranatt, P.P., Zeng, L., Smith, M.S., Chandran, B., 2005. ERK1/2 and mek1/2 induced by kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) early during infection of target cells are essential for expression of viral genes and for establishment of infection. J. Virol. 79, 10308–10329.

  • Shen, H., Wu, N., Wang, Y., Han, X., Zheng, Q., Cai, X., Zhang, H., Zhao, M., 2017. JNK inhibitor SP600125 aparaquat-induced alung injury: an in vivo and in vitro study. Inflammation 40, 1319–1330.

  • Stevens, J.G., Wagner, E., Devi-Rao, G., Cook, M., Feldman, L., 1987. RNA complementary to a herpesvirus alpha gene mRNA is prominent in latently infected neurons. Science 235, 1056–1059.

  • Tombacz, D., Toth, J.S., Boldogkoi, Z., 2011. Deletion of the virion host shut: off gene of pseudorabies virus results in selective upregulation of the expression of early viral genes in the late stage of infection. Genomics 98, 15–25.

  • van Dam, H., Wilhelm, D., Herr, I., Steffen, A., Herrlich, P., Angel, P., 1995. ATF-2 is preferentially activated by stress-activated protein kinases to mediate c-jun induction in response to genotoxic agents. EMBO J. 14, 1798–1811.

  • Wang, L., Payton, R., Dai, W., Lu, L., 2011. Hyperosmotic Stress-induced ATF-2 Activation through Polo-like Kinase 3 in Human Corneal Epithelial Cells. J. Biol. Chem. 286, 1951–1958.

  • Wang, X., Wu, C.-X., Song, X.-R., Chen, H.-C., Liu, Z.-F., 2017. Comparison of pseudorabies virus China reference strain with emerging variants reveals independent virus evolution within specific geographic regions. Virology 506, 92–98.

  • Wang, X., Zhang, M.-M., Yan, K., Tang, Q., Wu, Y.-Q., He, W.-B., Chen, H.-C., Liu, Z.-F., 2018. The full-length microRNA cluster in the intron of large latency transcript is associated with the virulence of pseudorabies virus. Virology 520, 59–66.

  • Wojcechowskyj, J.A., Didigu, C.A., Lee, J.Y., Parrish, N.F., Sinha, R., Hahn, B.H., Bushman, F.D., Jensen, S.T., Seeholzer, S.H., Doms, R.W., 2013. Quantitative phosphoproteomics reveals extensive cellular reprogramming during HIV-1 entry. Cell Host Microbe 13, 613–623.

  • Wu, Y.Q., Chen, D.J., He, H.B., Chen, D.S., Chen, L.L., Chen, H.C., Liu, Z.F., 2012. Pseudorabies virus infected porcine epithelial cell line generates a diverse set of host microRNAs and a special cluster of viral microRNAs. PLoS One 7, e30988.

  • Xie, S., Shen, B., Zhang, C., Huang, X., Zhang, Y., 2014. sgRNAcas9: a software package for designing CRISPR sgRNA and evaluating potential off-target cleavage sites. PLoS One 9, e100448.

  • Xing, J., Liang, J., Liu, S., Huang, L., Hu, P., Liu, L., Liao, M., Qi, W., 2021. Japanese encephalitis virus restricts hmgb1 expression to maintain mapk pathway activation for viral replication. Vet. Microbiol. 262, 109237.

  • Yan, K., Liu, J., Guan, X., Yin, Y.-X., Peng, H., Chen, H.-C., Liu, Z.-F., 2019. The ctterminus of ttegument protein pUL 21 contributes to pseudorabies virus neuroinvasion. J. Virol. 93 e02052-2018.

  • Yang, S., Pei, Y., Zhao, A., 2017. iTRAQ-based proteomic analysis of porcine kidney epithelial PK15 cells infected with pseudorabies virus. Sci. Rep. 7, 45922.

  • Yeh, C.J., Lin, P.Y., Liao, M.H., Liu, H.J., Lee, J.W., Chiu, S.J., Hsu, H.Y., Shih, W.L., 2008. TNF-alpha mediates pseudorabies virus-induced apoptosis via the activation of p38 MAPK and JNK/SAPK signaling. Virology 381, 55–66.

  • Yin, Y., Romero, N., Favoreel, H.W., 2021. Pseudorabies virus inhibits type I and type III interferon-induced signaling via proteasomal degradation of janus kinases. J. Virol. 95, e0079321.

  • Yu, X.L., Zhou, Z., Hu, D., Zhang, Q., Han, T., Li, X., Gu, X., Yuan, L., Zhang, S., Wang, B., 2014. Pathogenic pseudorabies virus, china, 2012. Emerg. Infect. Dis. 20, 102–104.

  • Yuan, Z., Gong, S., Luo, J., Zheng, Z., Song, B., Ma, S., Guo, J., Hu, C., Thiel, G., Vinson, C., Hu, C.D., Wang, Y., Li, M., 2009. Opposing roles for ATF2 and c-Fos in c-Junmediated neuronal apoptosis. Mol. Cell Biol. 29, 2431–2442.

  • Yuan, J, Liu, X., Wu, A.W., McGonagill, P.W., Keller, M.J., Galle, C.S., Meier, J.L., 2009. Breaking human cytomegalovirus major immediate-early gene silence by vasoactive intestinal peptide stimulation of the protein kinase a-creb-torc2 signaling cascade in human pluripotent embryonal ntera2 cells. J. Virol. 83, 6391–6403.

  • Zachos, G., Clements, B., Conner, J., 1999. Herpes simplex virus type 1 infection stimulates p38/c-Jun N-terminal mitogen-activated protein kinase pathways and activates transcription factor AP-1. J. Biol. Chem. 274, 5097–5103.

  • Zhu, Z.X., Li, W.W., Zhang, X.L., Wang, C.C., Gao, L.L., Yang, F., Cao, W.J., Li, K.L., Tian, H., Liu, X.T., Zhang, K.S., Zheng, H.X., 2020. Foot-and-mouth disease virus capsid protein vp1 interacts with host ribosomal protein sa to maintain activation of the mapk signal pathway and promote virus replication. J. Virol. 94, e01350-19.