{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:10:23Z","timestamp":1790208623747,"version":"4.1.0"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC2300200, 2023YFC2307801, 2021YFD1800105-1, 2025YFC2311800, 2024YFD1800502"],"award-info":[{"award-number":["2021YFC2300200, 2023YFC2307801, 2021YFD1800105-1, 2025YFC2311800, 2024YFD1800502"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32270157,82222040"],"award-info":[{"award-number":["32270157,82222040"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CAS Project for Young scientists in Basic Research","award":["YSBR-083"],"award-info":[{"award-number":["YSBR-083"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,9,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      African swine fever (ASF) has caused a devastating pandemic among domestic and wild swine, leading to significant economic losses in the global swine industry. Recombinant live-attenuated vaccines are a potential option for the control of ASF. However, safe and effective vaccines against the ASF virus (ASFV) are not yet commercially available, and thus, additional vaccine candidates still need to be developed. In this study, we demonstrate that the simultaneous deletion of the ASFV genes\n                      <jats:italic toggle=\"yes\">CD2v<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">A137R<\/jats:italic>\n                      from the highly virulent isolate ASFV HuB\/HH\/2019 substantially attenuated the virulence in swine. All pigs (4\/4) infected with 10\n                      <jats:sup>5<\/jats:sup>\n                      TCID\n                      <jats:sub>50<\/jats:sub>\n                      doses of the double gene deletion virus HuB\/HH\/2019\u0394\n                      <jats:italic toggle=\"yes\">CD2v<\/jats:italic>\n                      \u0394\n                      <jats:italic toggle=\"yes\">A137R<\/jats:italic>\n                      (HuB\u0394\n                      <jats:italic toggle=\"yes\">CD2v<\/jats:italic>\n                      \u0394\n                      <jats:italic toggle=\"yes\">A137R<\/jats:italic>\n                      ) remained healthy during a 27-day observation period, with no fevers (&gt;40.5\u00b0C) observed. Cases of viremia were mild and cleared by 24 days post-inoculation (dpi). Antibodies against ASFV p30 were induced, and the inoculated pigs were well-protected against homologous challenges. All inoculated pigs survived after being challenged with 10\n                      <jats:sup>2<\/jats:sup>\n                      HAD\n                      <jats:sub>50<\/jats:sub>\n                      ASFV HuB\/HH\/2019, and no fever or clinical symptoms developed during the 22-day monitoring period. In contrast, all control group pigs died before 11 dpi (2\/2). Cytokine assays and RNA sequencing revealed mild responses elicited by HuB\u0394\n                      <jats:italic toggle=\"yes\">CD2v<\/jats:italic>\n                      \u0394\n                      <jats:italic toggle=\"yes\">A137R<\/jats:italic>\n                      . Successful innate and passive immune responses were also triggered. The findings suggest that deletion of the\n                      <jats:italic toggle=\"yes\">CD2v<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">A137R<\/jats:italic>\n                      genes can attenuate ASFV, and the deletion mutant virus HuB\u0394\n                      <jats:italic toggle=\"yes\">CD2v<\/jats:italic>\n                      \u0394\n                      <jats:italic toggle=\"yes\">A137R<\/jats:italic>\n                      is a promising vaccine candidate.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The emergence of ASF has caused substantial economic losses in the global pig industry. In light of this, the development of a safe and effective vaccine is crucial to control the spread of ASF. In this study, a live-attenuated ASFV strain was developed by simultaneously knocking out the viral genes\n                        <jats:italic toggle=\"yes\">CD2v<\/jats:italic>\n                        and\n                        <jats:italic toggle=\"yes\">A137R<\/jats:italic>\n                        . The mutant virus exhibited weakened virulence in pigs, elicited robust humoral and cellular immunity, and conferred protection upon challenge with high doses of the parental virus. Notably, no fever or clinical symptoms were observed during a 27-day monitoring period. Consequently, our research presents a highly promising candidate strain for a live-attenuated vaccine, offering a significant step forward in the quest for effective prevention measures. Additionally, the identification of these specific gene targets opens up avenues for further exploration and refinement of strategies aimed at combating ASF outbreaks.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00262-25","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T13:00:11Z","timestamp":1756904411000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["An attenuated African swine fever virus with deletions of the\n                    <i>CD2v<\/i>\n                    and\n                    <i>A137R<\/i>\n                    genes offers complete protection against homologous challenge in pigs"],"prefix":"10.1128","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5513-1277","authenticated-orcid":false,"given":"Guorui","family":"Peng","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University","place":["Beijing, China"]},{"id":[{"id":"https:\/\/ror.org\/03jt74a36","id-type":"ROR","asserted-by":"publisher"}],"name":"China\/WOAH Reference Laboratory for Classical Swine Fever, China Institute of Veterinary Drug Control","place":["Beijing, China"]},{"id":[{"id":"https:\/\/ror.org\/02p1jz666","id-type":"ROR","asserted-by":"publisher"}],"name":"CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2001-1343","authenticated-orcid":false,"given":"Xin","family":"Zhao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02p1jz666","id-type":"ROR","asserted-by":"publisher"}],"name":"CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingqi","family":"Zou","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03jt74a36","id-type":"ROR","asserted-by":"publisher"}],"name":"China\/WOAH Reference Laboratory for Classical Swine Fever, China Institute of Veterinary Drug Control","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02p1jz666","id-type":"ROR","asserted-by":"publisher"}],"name":"CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Zhao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03jt74a36","id-type":"ROR","asserted-by":"publisher"}],"name":"China\/WOAH Reference Laboratory for Classical Swine Fever, China Institute of Veterinary Drug Control","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuezhi","family":"Zuo","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University","place":["Beijing, China"]},{"id":[{"id":"https:\/\/ror.org\/03jt74a36","id-type":"ROR","asserted-by":"publisher"}],"name":"China\/WOAH Reference Laboratory for Classical Swine Fever, China Institute of Veterinary Drug Control","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuguang","family":"Tan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02p1jz666","id-type":"ROR","asserted-by":"publisher"}],"name":"CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruizhi","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University","place":["Beijing, China"]},{"id":[{"id":"https:\/\/ror.org\/03jt74a36","id-type":"ROR","asserted-by":"publisher"}],"name":"China\/WOAH Reference Laboratory for Classical Swine Fever, China Institute of Veterinary Drug Control","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Guan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03jt74a36","id-type":"ROR","asserted-by":"publisher"}],"name":"China\/WOAH Reference Laboratory for Classical Swine Fever, China Institute of Veterinary Drug Control","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3608-4106","authenticated-orcid":true,"given":"Shihua","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02p1jz666","id-type":"ROR","asserted-by":"publisher"}],"name":"CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Xu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03jt74a36","id-type":"ROR","asserted-by":"publisher"}],"name":"China\/WOAH Reference Laboratory for Classical Swine Fever, China Institute of Veterinary Drug Control","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingju","family":"Xia","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03jt74a36","id-type":"ROR","asserted-by":"publisher"}],"name":"China\/WOAH Reference Laboratory for Classical Swine Fever, China Institute of Veterinary Drug Control","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoai","family":"Xu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03jt74a36","id-type":"ROR","asserted-by":"publisher"}],"name":"China\/WOAH Reference Laboratory for Classical Swine Fever, China Institute of Veterinary Drug Control","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Xu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03jt74a36","id-type":"ROR","asserted-by":"publisher"}],"name":"China\/WOAH Reference Laboratory for Classical Swine Fever, China Institute of Veterinary Drug Control","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Zhu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03jt74a36","id-type":"ROR","asserted-by":"publisher"}],"name":"China\/WOAH Reference Laboratory for Classical Swine Fever, China Institute of Veterinary Drug Control","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4128-1043","authenticated-orcid":true,"given":"Jinhua","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2715-6122","authenticated-orcid":false,"given":"Yebing","family":"Liu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03jt74a36","id-type":"ROR","asserted-by":"publisher"}],"name":"China\/WOAH Reference Laboratory for Classical Swine Fever, China Institute of Veterinary Drug Control","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3869-615X","authenticated-orcid":true,"given":"George Fu","family":"Gao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02p1jz666","id-type":"ROR","asserted-by":"publisher"}],"name":"CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0368-1742(21)80031-4"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2020.198099"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/tbed.12700"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/v9050103"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0192565"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-021-1904-4"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2021.1999779"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38868-w"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2012.10.020"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2019.11.004"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01536-23"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01957-21"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2024.2377599"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01139-21"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01428-17"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.67.9.5312-5320.1993"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01994-10"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/v12101185"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.4.2881-2889.1998"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-024-00845-9"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.3390\/v13081480"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2200813"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2018.03.040"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.80058-0"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1361531"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hlife.2023.12.005"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2021.105024"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/tbed.14329"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01058-17"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.3390\/v12060615"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-57455-3"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.3390\/v14091917"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-020-1657-9"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2210808120"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00969-15"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02017-19"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01419-21"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01199-21"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01760-16"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.3390\/v14092024"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01500-21"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2022.2148560"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12985-023-02111-1"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz114"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.00262-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.00262-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T21:51:08Z","timestamp":1758664268000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/jvi.00262-25"}},"subtitle":[],"editor":[{"given":"Jae U.","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,23]]},"references-count":47,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9,23]]}},"alternative-id":["10.1128\/jvi.00262-25"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00262-25","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,23]]},"assertion":[{"value":"2025-02-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00262-25"}}