{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:10:52Z","timestamp":1792714252817,"version":"4.5.0"},"reference-count":83,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,7,21]],"date-time":"2020-07-21T00:00:00Z","timestamp":1595289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM113117; R01AI143709"],"award-info":[{"award-number":["P20GM113117; R01AI143709"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Four decades after the eradication of smallpox, poxviruses continue to threaten the health of humans and other animals. Vaccinia virus (VACV) was used as the vaccine that successfully eradicated smallpox and is a prototypic member of the poxvirus family. Many cellular pathways play critical roles in productive poxvirus replication. These pathways provide opportunities to expand the arsenal of poxvirus antiviral development by targeting the cellular functions required for efficient poxvirus replication. In this study, we developed and optimized a secreted Gaussia luciferase-based, simplified assay procedure suitable for high throughput screening. Using this procedure, we screened a customized compound library that contained over 3200 bioactives and FDA (Food and Drug Administration)-approved chemicals, most having known cellular targets, for their inhibitory effects on VACV replication. We identified over 140 compounds that suppressed VACV replication. Many of these hits target cellular pathways previously reported to be required for efficient VACV replication, validating the effectiveness of our screening. Importantly, we also identified hits that target cellular functions with previously unknown roles in the VACV replication cycle. Among those in the latter category, we verified the antiviral role of several compounds targeting the janus kinase\/signal transducer and activator of transcription-3 (JAK\/STAT3) signaling pathway by showing that STAT3 inhibitors reduced VACV replication. Our findings identify pathways that are candidates for use in the prevention and treatment of poxvirus infections and additionally provide a foundation to investigate diverse cellular pathways for their roles in poxvirus replications.<\/jats:p>","DOI":"10.3390\/vaccines8030401","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T03:23:16Z","timestamp":1595388196000},"page":"401","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Identification of Vaccinia Virus Inhibitors and Cellular Functions Necessary for Efficient Viral Replication by Screening Bioactives and FDA-Approved Drugs"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6141-8775","authenticated-orcid":false,"given":"Chen","family":"Peng","sequence":"first","affiliation":[{"name":"Division of Biology, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Division of Biology, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Cao","sequence":"additional","affiliation":[{"name":"Division of Biology, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Pant","sequence":"additional","affiliation":[{"name":"Division of Biology, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8496-7718","authenticated-orcid":false,"given":"Marlene L.","family":"Campos Guerrero","sequence":"additional","affiliation":[{"name":"Division of Biology, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"McDonald","sequence":"additional","affiliation":[{"name":"High Throughput Screening Laboratory, University of Kansas, Lawrence, KS 66045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuradha","family":"Roy","sequence":"additional","affiliation":[{"name":"High Throughput Screening Laboratory, University of Kansas, Lawrence, KS 66045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilong","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Biology, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,21]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2011). Chapter 1: Smallpox: Eradicating an ancient scourge. Bugs, Drugs and Smoke, WHO Press."},{"key":"ref_2","unstructured":"Moss, B. (2013). Poxviridae, Fields Virology, Lippincott Williams & Wilkins. [6th ed.]."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Noyce, R.S., Lederman, S., and Evans, D.H. (2018). Construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0188453"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Beer, E.M., and Rao, V.B. (2019). A systematic review of the epidemiology of human monkeypox outbreaks and implications for outbreak strategy. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007791"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.idc.2019.03.001","article-title":"Human Monkeypox: Epidemiologic and Clinical Characteristics, Diagnosis, and Prevention","volume":"33","author":"Petersen","year":"2019","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_6","unstructured":"Centers for Disease Control and Prevention (CDC) (2003). Update: Multistate outbreak of monkeypox\u2014Illinois, Indiana, Kansas, Missouri, Ohio, and Wisconsin, 2003. MMWR Morb. Mortal Wkly Rep., 52, 642\u2013646."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1800509","DOI":"10.2807\/1560-7917.ES.2018.23.38.1800509","article-title":"Two cases of monkeypox imported to the United Kingdom, September 2018","volume":"23","author":"Vaughan","year":"2018","journal-title":"Eurosurveillance"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1016\/S1473-3099(19)30537-7","article-title":"A case of imported Monkeypox in Singapore","volume":"19","author":"Ng","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"980","DOI":"10.3201\/eid2505.190076","article-title":"Diagnosis of Imported Monkeypox, Israel, 2018","volume":"25","author":"Erez","year":"2019","journal-title":"Emerg. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"373","DOI":"10.2147\/CCID.S187224","article-title":"Molluscum contagiosum: An update and review of new perspectives in etiology, diagnosis, and treatment","volume":"12","author":"Downey","year":"2019","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1097\/00001432-200404000-00003","article-title":"Zoonotic poxvirus infections in humans","volume":"17","year":"2004","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Oliveira, G.P., Rodrigues, R.A.L., Lima, M.T., Drumond, B.P., and Abrah\u00e3o, J.S. (2017). Poxvirus Host Range Genes and Virus-Host Spectrum: A Critical Review. Viruses, 9.","DOI":"10.3390\/v9110331"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.vetmic.2009.08.026","article-title":"Zoonotic poxviruses","volume":"140","author":"Essbauer","year":"2010","journal-title":"Vet. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.antiviral.2019.06.005","article-title":"The development and approval of tecoviromat (TPOXX\u00ae), the first antiviral against smallpox","volume":"168","author":"Merchlinsky","year":"2019","journal-title":"Antivir. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e221","DOI":"10.1016\/S1473-3099(18)30788-6","article-title":"Assessing a drug for an eradicated human disease: US Food and Drug Administration review of tecovirimat for the treatment of smallpox","volume":"19","author":"Harrington","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.antiviral.2018.02.005","article-title":"In vitro susceptibility to ST-246 and Cidofovir corroborates the phylogenetic separation of Brazilian Vaccinia virus into two clades","volume":"152","author":"Pires","year":"2018","journal-title":"Antivir. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e01683","DOI":"10.1128\/AAC.01683-19","article-title":"Drug Development against Smallpox: Present and Future","volume":"64","author":"Delaune","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7310","DOI":"10.1128\/JVI.00355-12","article-title":"Mutations conferring resistance to viral DNA polymerase inhibitors in camelpox virus give different drug-susceptibility profiles in vaccinia virus","volume":"86","author":"Duraffour","year":"2012","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/nrd.2017.162","article-title":"Host-directed therapies for bacterial and viral infections","volume":"17","author":"Kaufmann","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e01834","DOI":"10.1128\/JVI.01834-18","article-title":"Asparagine Is a Critical Limiting Metabolite for Vaccinia Virus Protein Synthesis during Glutamine Deprivation","volume":"93","author":"Pant","year":"2019","journal-title":"J. Virol."},{"key":"ref_21","first-page":"45","article-title":"Inhibition of plaque formation of vaccinia virus by cytosine arabinoside hydrochloride","volume":"45","author":"Renis","year":"1962","journal-title":"Bacteriol. Proc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1128\/JVI.76.3.1379-1390.2002","article-title":"Molecular chaperone Hsp90 is important for vaccinia virus growth in cells","volume":"76","author":"Hung","year":"2002","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/s41564-018-0288-2","article-title":"Vaccinia virus hijacks EGFR signalling to enhance virus spread through rapid and directed infected cell motility","volume":"4","author":"Beerli","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.virusres.2015.01.024","article-title":"The role of signalling and the cytoskeleton during Vaccinia Virus egress","volume":"209","author":"Leite","year":"2015","journal-title":"Virus Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e00784","DOI":"10.1128\/JVI.00784-19","article-title":"mTOR Dysregulation by Vaccinia Virus F17 Controls Multiple Processes with Varying Roles in Infection","volume":"93","author":"Meade","year":"2019","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1016\/j.cell.2018.06.053","article-title":"Poxviruses Evade Cytosolic Sensing through Disruption of an mTORC1-mTORC2 Regulatory Circuit","volume":"174","author":"Meade","year":"2018","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.virusres.2004.01.028","article-title":"YY1 is recruited to the cytoplasm of vaccinia virus-infected human macrophages by the Crm1 system","volume":"102","author":"Slezak","year":"2004","journal-title":"Virus Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.1128\/JVI.01986-08","article-title":"Inhibition of the ubiquitin-proteasome system prevents vaccinia virus DNA replication and expression of intermediate and late genes","volume":"83","author":"Satheshkumar","year":"2009","journal-title":"J. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3519","DOI":"10.1073\/pnas.1300708110","article-title":"Human genome-wide RNAi screen reveals a role for nuclear pore proteins in poxvirus morphogenesis","volume":"110","author":"Sivan","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.celrep.2012.09.003","article-title":"RNAi screening reveals proteasome- and Cullin3-dependent stages in vaccinia virus infection","volume":"2","author":"Mercer","year":"2012","journal-title":"Cell Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3086","DOI":"10.1099\/jgv.0.000946","article-title":"Vaccinia virus protein A49 activates Wnt signalling by targetting the E3 ligase \u03b2-TrCP","volume":"98","author":"Smith","year":"2017","journal-title":"J. Gen. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.virol.2004.08.013","article-title":"The vaccinia virus B1R kinase induces p53 downregulation by an Mdm2-dependent mechanism","volume":"328","author":"Santos","year":"2004","journal-title":"Virology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1177\/095632020601700201","article-title":"Synergistic Combination Effect of Cidofovir and Idoxuridine on Vaccinia Virus Replication","volume":"17","author":"Remichkova","year":"2016","journal-title":"Antivir. Chem. Chemother."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"a010199","DOI":"10.1101\/cshperspect.a010199","article-title":"Poxvirus DNA replication","volume":"5","author":"Moss","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"891","DOI":"10.2217\/fvl.13.76","article-title":"Orthopoxvirus inhibitors that are active in animal models: An update from 2008 to 2012","volume":"8","author":"Smee","year":"2013","journal-title":"Future Virol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Gammon, D.B., Gowrishankar, B., Duraffour, S., Andrei, G., Upton, C., and Evans, D.H. (2010). Vaccinia virus-encoded ribonucleotide reductase subunits are differentially required for replication and pathogenesis. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000984"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/0168-1702(88)90027-5","article-title":"Inhibition of vaccinia virus replication by nicotinamide: Evidence for ADP-ribosylation of viral proteins","volume":"9","author":"Child","year":"1988","journal-title":"Virus Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e01385","DOI":"10.1128\/JVI.01385-17","article-title":"Vaccinia Virus Encodes a Novel Inhibitor of Apoptosis That Associates with the Apoptosome","volume":"91","author":"Ryerson","year":"2017","journal-title":"J. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0168-1702(98)00105-1","article-title":"Vaccinia virus-induced apoptosis in immature B lymphocytes: Role of cellular Bcl-2","volume":"58","author":"Baixeras","year":"1998","journal-title":"Virus Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1089\/vim.2005.18.224","article-title":"Changes in Bcl-2 expression in vaccinia virus-infected human peripheral blood monocytes","volume":"18","author":"Kowalczyk","year":"2005","journal-title":"Viral Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1006\/viro.2001.1154","article-title":"Vaccinia virus E3L interferon resistance protein inhibits the interferon-induced adenosine deaminase A-to-I editing activity","volume":"289","author":"Liu","year":"2001","journal-title":"Virology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1128\/AAC.6.5.630","article-title":"Effect of adenosine deaminase upon the antiviral activity in vitro of adenine arabinoside for vaccinia virus","volume":"6","author":"Connor","year":"1974","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Chen, R.A.J., Ryzhakov, G., Cooray, S., Randow, F., and Smith, G.L. (2008). Inhibition of IkappaB kinase by vaccinia virus virulence factor B14. PLoS Pathog., 4.","DOI":"10.1371\/journal.ppat.0040022"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"11997","DOI":"10.1073\/pnas.1816399116","article-title":"Histone deacetylase 4 promotes type I interferon signaling, restricts DNA viruses, and is degraded via vaccinia virus protein C6","volume":"116","author":"Lu","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Greseth, M.D., and Traktman, P. (2014). De novo fatty acid biosynthesis contributes significantly to establishment of a bioenergetically favorable environment for vaccinia virus infection. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004021"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1084\/jem.20022201","article-title":"Steroid hormone synthesis by vaccinia virus suppresses the inflammatory response to infection","volume":"197","author":"Reading","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1099\/vir.0.19271-0","article-title":"Vaccinia virus cores are transported on microtubules","volume":"84","author":"Carter","year":"2003","journal-title":"J. Gen. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"11651","DOI":"10.1128\/JVI.75.23.11651-11663.2001","article-title":"Vaccinia virus intracellular movement is associated with microtubules and independent of actin tails","volume":"75","author":"Ward","year":"2001","journal-title":"J. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1038\/ncb1101-992","article-title":"Kinesin-dependent movement on microtubules precedes actin-based motility of vaccinia virus","volume":"3","author":"Rietdorf","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1083\/jcb.200104124","article-title":"Vaccinia virus utilizes microtubules for movement to the cell surface","volume":"154","author":"Hollinshead","year":"2001","journal-title":"J. Cell Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.virol.2016.12.011","article-title":"Viral exploitation of the MEK\/ERK pathway\u2014A tale of vaccinia virus and other viruses","volume":"507","author":"Bonjardim","year":"2017","journal-title":"Virology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.1099\/jgv.0.000525","article-title":"Multiple Bcl-2 family immunomodulators from vaccinia virus regulate MAPK\/AP-1 activation","volume":"97","author":"Torres","year":"2016","journal-title":"J. Gen. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1042\/BJ20031375","article-title":"The vaccinia virus-stimulated mitogen-activated protein kinase (MAPK) pathway is required for virus multiplication","volume":"381","author":"Andrade","year":"2004","journal-title":"Biochem. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1111\/tra.12290","article-title":"Vaccinia Virus Infection Requires Maturation of Macropinosomes","volume":"16","author":"Rizopoulos","year":"2015","journal-title":"Traffic"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1089\/jir.2011.0100","article-title":"Glomulin: A permissivity factor for vaccinia virus infection","volume":"32","author":"Rahbar","year":"2012","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1634\/stemcells.2007-0461","article-title":"Vaccinia virus infection modulates the hematopoietic cell compartments in the bone marrow","volume":"26","author":"Singh","year":"2008","journal-title":"Stem Cells"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2971","DOI":"10.1007\/s00705-017-3446-6","article-title":"c-Jun integrates signals from both MEK\/ERK and MKK\/JNK pathways upon vaccinia virus infection","volume":"162","author":"Leite","year":"2017","journal-title":"Arch. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/cgt.2008.32","article-title":"JNK-deficiency enhanced oncolytic vaccinia virus replication and blocked activation of double-stranded RNA-dependent protein kinase","volume":"15","author":"Hu","year":"2008","journal-title":"Cancer Gene Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"6677","DOI":"10.1128\/JVI.06860-11","article-title":"Integrin \u03b21 mediates vaccinia virus entry through activation of PI3K\/Akt signaling","volume":"86","author":"Izmailyan","year":"2012","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"McNulty, S., Bornmann, W., Schriewer, J., Werner, C., Smith, S.K., Olson, V.A., Damon, I.K., Buller, R.M., Heuser, J., and Kalman, D. (2010). Multiple phosphatidylinositol 3-kinases regulate vaccinia virus morphogenesis. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010884"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6883","DOI":"10.1128\/JVI.00245-09","article-title":"Activation of the PI3K\/Akt pathway early during vaccinia and cowpox virus infections is required for both host survival and viral replication","volume":"83","author":"Soares","year":"2009","journal-title":"J. Virol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3988","DOI":"10.1128\/JVI.02284-08","article-title":"PI3K signaling regulates rapamycin-insensitive translation initiation complex formation in vaccinia virus-infected cells","volume":"83","author":"Zaborowska","year":"2009","journal-title":"J. Virol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/j.1462-5822.2005.00613.x","article-title":"Abl collaborates with Src family kinases to stimulate actin-based motility of vaccinia virus","volume":"8","author":"Newsome","year":"2006","journal-title":"Cell Microbiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1126\/science.1101509","article-title":"SRC mediates a switch from microtubule- to actin-based motility of vaccinia virus","volume":"306","author":"Newsome","year":"2004","journal-title":"Science"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.celrep.2013.06.028","article-title":"Vaccinia virus entry is followed by core activation and proteasome-mediated release of the immunomodulatory effector VH1 from lateral bodies","volume":"4","author":"Schmidt","year":"2013","journal-title":"Cell Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5922","DOI":"10.1128\/JVI.02723-07","article-title":"Vaccinia virus DNA ligase recruits cellular topoisomerase II to sites of viral replication and assembly","volume":"82","author":"Lin","year":"2008","journal-title":"J. Virol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/S0140-6736(94)90750-1","article-title":"Quality of life and survival with continuous hepatic-artery floxuridine infusion for colorectal liver metastases","volume":"344","author":"Earlam","year":"1994","journal-title":"Lancet"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Mazzucconi, M.G., Baldacci, E., Latagliata, R., Breccia, M., Paoloni, F., Di Veroli, A., Cedrone, M., Anaclerico, B., Villiv\u00e0, N., and Porrini, R. (2020). Anagrelide in Essential Thrombocythemia (ET): Results from 150 patients over 25 years by the \u2019Ph1-negative Myeloproliferative Neoplasms Latium Group\u2019. Eur. J. Haematol., ejh.13454.","DOI":"10.1111\/ejh.13454"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.ejps.2019.03.026","article-title":"Tyrosine kinase inhibitor conjugated quantum dots for non-small cell lung cancer (NSCLC) treatment","volume":"133","author":"Kulkarni","year":"2019","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1038\/nri1226","article-title":"Regulation of JAK-STAT signalling in the immune system","volume":"3","author":"Shuai","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"21","DOI":"10.4049\/jimmunol.1401867","article-title":"Mechanisms of Jak\/STAT signaling in immunity and disease","volume":"194","author":"Villarino","year":"2015","journal-title":"J. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.immuni.2012.03.014","article-title":"JAK and STAT signaling molecules in immunoregulation and immune-mediated disease","volume":"36","author":"Plenge","year":"2012","journal-title":"Immunity"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1476-9255-2-12","article-title":"Heat shock protein and heat shock factor 1 expression and localization in vaccinia virus infected human monocyte derived macrophages","volume":"2","author":"Kowalczyk","year":"2005","journal-title":"J. Inflamm. (Lond.)"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/s41580-019-0199-y","article-title":"mTOR at the nexus of nutrition, growth, ageing and disease","volume":"21","author":"Liu","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Le Sage, V., Cinti, A., Amorim, R., and Mouland, A.J. (2016). Adapting the Stress Response: Viral Subversion of the mTOR Signaling Pathway. Viruses, 8.","DOI":"10.3390\/v8060152"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"He, Y., Fisher, R., Chowdhury, S., Sultana, I., Pereira, C.P., and Bray, M. (2014). Vaccinia virus induces rapid necrosis in keratinocytes by a STAT3-dependent mechanism. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0113690"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"8807","DOI":"10.1016\/j.vaccine.2007.10.040","article-title":"Genomic differences of Vaccinia virus clones from Dryvax smallpox vaccine: The Dryvax-like ACAM2000 and the mouse neurovirulent Clone-3","volume":"25","author":"Osborne","year":"2007","journal-title":"Vaccine"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"4569","DOI":"10.1016\/j.vaccine.2013.07.057","article-title":"Attenuation and immunogenicity of host-range extended modified vaccinia virus Ankara recombinants","volume":"31","author":"Melamed","year":"2013","journal-title":"Vaccine"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2009.06.006","article-title":"Vaccinia virus vaccines: Past, present and future","volume":"84","author":"Jacobs","year":"2009","journal-title":"Antivir. Res."},{"key":"ref_80","first-page":"e01570","article-title":"Full Genome Sequence of the Western Reserve Strain of Vaccinia Virus Determined by Third-Generation Sequencing","volume":"6","author":"Snyder","year":"2018","journal-title":"Genome Announc."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Liu, R., Mendez-Rios, J.D., Peng, C., Xiao, W., Weisberg, A.S., Wyatt, L.S., and Moss, B. (2019). SPI-1 is a missing host-range factor required for replication of the attenuated modified vaccinia Ankara (MVA) vaccine vector in human cells. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007710"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3759","DOI":"10.1073\/pnas.1921098117","article-title":"Repair of a previously uncharacterized second host-range gene contributes to full replication of modified vaccinia virus Ankara (MVA) in human cells","volume":"117","author":"Peng","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Moser, T.S., Jones, R.G., Thompson, C.B., Coyne, C.B., and Cherry, S. (2010). A kinome RNAi screen identified AMPK as promoting poxvirus entry through the control of actin dynamics. 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