{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T19:09:29Z","timestamp":1789758569412,"version":"4.0.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014573","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000}}],"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012165","name":"Key Technologies Research and Development Program","doi-asserted-by":"publisher","award":["2021YFD1800100"],"award-info":[{"award-number":["2021YFD1800100"]}],"id":[{"id":"10.13039\/501100012165","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010038","name":"Earmarked Fund for China Agriculture Research System","doi-asserted-by":"publisher","award":["CARS-35"],"award-info":[{"award-number":["CARS-35"]}],"id":[{"id":"10.13039\/501100010038","id-type":"DOI","asserted-by":"publisher"}]},{"name":"2115 Talent Development Program of China Agricultural University","id":[{"id":"https:\/\/ror.org\/04v3ywz14","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    African swine fever virus (ASFV) is a devastating pathogen that poses a severe threat to the global swine industry. ASFV primarily targets the porcine monocyte-macrophage system, which is crucial for defending against bacterial infections via phagocytosis and subsequent intracellular degradation. Clinically, ASFV infection can be complicated by severe secondary bacterial infections. This creates a compelling paradox: while prior\n                    <jats:italic>in vitro<\/jats:italic>\n                    studies indicate that ASFV actually increases the phagocytic activity of porcine alveolar macrophages (PAMs), clinical observations frequently report severe secondary bacterial infections. This contradiction led us to hypothesize that the downstream intracellular bactericidal clearance might be compromised. Here, utilizing an\n                    <jats:italic>in vitro<\/jats:italic>\n                    co-infection model, it was demonstrated that ASFV significantly impairs the bactericidal capacity of PAMs against representative bacteria (\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    ,\n                    <jats:italic>Glaesserella parasuis, and Streptococcus suis<\/jats:italic>\n                    ), facilitating their intracellular survival and persistence. Although ASFV infection triggers massive reactive oxygen species (ROS) production, this oxidative stress remains functionally ineffective because phagolysosomal acidification and structural integrity are profoundly impaired. Mechanistically, at the late stage of infection, ASFV launches a multipronged assault on the endolysosomal network. Structurally, ASFV inhibits phagosomal and lysosomal acidification while inducing oxidative stress-driven severe lysosomal membrane permeabilization (LMP), leading to reduced phagolysosome volume and physical depletion of the lysosomal pool. Molecularly, ASFV impairs degradative capacity through the transcriptional suppression and blunted lysosomal enrichment of vacuolar (H\n                    <jats:sup>+<\/jats:sup>\n                    ) ATPase (V-ATPase) subunits, alongside the disruption of lysosomal protease cathepsin D (CTSD) maturation. Furthermore, systematic screening identified six core candidate viral proteins, including CP530R, D129R, E183L, O174L, Q706L, and QP509R, that profoundly suppress both\n                    <jats:italic>ATP6V0D<\/jats:italic>\n                    and\n                    <jats:italic>CTSK<\/jats:italic>\n                    transcription, further exacerbating this functional impairment. Collectively, our\n                    <jats:italic>in vitro<\/jats:italic>\n                    findings reveal that ASFV dismantles host phagolysosomal acidification, thereby neutralizing the microbicidal potential of infected macrophages and potentially converting them into a permissive niche for secondary bacterial pathogens. These observations provide critical new mechanistic insights that may help explain ASFV-associated immune dysfunction at the cellular level.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014573","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T17:43:15Z","timestamp":1789062195000},"page":"e1014573","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["African swine fever virus impairs porcine alveolar macrophages bactericidal function by disrupting lysosomal acidification and cathepsin activity"],"prefix":"10.1371","volume":"22","author":[{"given":"Zhen","family":"Xu","sequence":"first","affiliation":[{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["State Key Laboratory of Veterinary Public Health Safety, College of Veterinary Medicine"]},{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyang","family":"Shi","sequence":"additional","affiliation":[{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["State Key Laboratory of Veterinary Public Health Safety, College of Veterinary Medicine"]},{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Xiang","sequence":"additional","affiliation":[{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["State Key Laboratory of Veterinary Public Health Safety, College of Veterinary Medicine"]},{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runzhi","family":"Guo","sequence":"additional","affiliation":[{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["State Key Laboratory of Veterinary Public Health Safety, College of Veterinary Medicine"]},{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Wen","sequence":"additional","affiliation":[{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["State Key Laboratory of Veterinary Public Health Safety, College of Veterinary Medicine"]},{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajin","family":"Qu","sequence":"additional","affiliation":[{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["State Key Laboratory of Veterinary Public Health Safety, College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanlin","family":"Li","sequence":"additional","affiliation":[{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["State Key Laboratory of Veterinary Public Health Safety, College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiongqiong","family":"Zhou","sequence":"additional","affiliation":[{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["State Key Laboratory of Veterinary Public Health Safety, College of Veterinary Medicine"]},{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Gao","sequence":"additional","affiliation":[{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["State Key Laboratory of Veterinary Public Health Safety, College of Veterinary Medicine"]},{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongning","family":"Zhang","sequence":"additional","affiliation":[{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["State Key Laboratory of Veterinary Public Health Safety, College of Veterinary Medicine"]},{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinna","family":"Ge","sequence":"additional","affiliation":[{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["State Key Laboratory of Veterinary Public Health Safety, College of Veterinary Medicine"]},{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Han","sequence":"additional","affiliation":[{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["State Key Laboratory of Veterinary Public Health Safety, College of Veterinary Medicine"]},{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Guo","sequence":"additional","affiliation":[{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["State Key Laboratory of Veterinary Public Health Safety, College of Veterinary Medicine"]},{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8837-3965","authenticated-orcid":true,"given":"Lei","family":"Zhou","sequence":"additional","affiliation":[{"name":"China Agricultural University","place":["Beijing, P.R. China"],"department":["State Key Laboratory of Veterinary Public Health Safety, College of Veterinary Medicine"]},{"name":"China Agricultural University","place":["Beijing, P.R. 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China"],"department":["Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"ppat.1014573.ref001","doi-asserted-by":"crossref","first-page":"402","DOI":"10.3389\/fgene.2019.00402","article-title":"The genetics of life and death: virus-host interactions underpinning resistance to African swine fever, a viral hemorrhagic disease","volume":"10","author":"CL Netherton","year":"2019","journal-title":"Front Genet"},{"issue":"5","key":"ppat.1014573.ref002","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.1111\/tbed.14039","article-title":"African swine fever spread across Asia, 2018-2019","volume":"68","author":"E Mighell","year":"2021","journal-title":"Transbound Emerg 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Yuan","year":"2024","journal-title":"Vet Microbiol"},{"issue":"4","key":"ppat.1014573.ref022","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00789-20","article-title":"African swine fever virus protein pE199L mediates virus entry by enabling membrane fusion and core penetration","volume":"11","author":"T Matamoros","year":"2020","journal-title":"mBio"},{"issue":"23","key":"ppat.1014573.ref023","doi-asserted-by":"crossref","first-page":"12290","DOI":"10.1128\/JVI.01333-09","article-title":"The African swine fever virus virion membrane protein pE248R is required for virus infectivity and an early postentry event","volume":"83","author":"I Rodr\u00edguez","year":"2009","journal-title":"J Virol"},{"issue":"6","key":"ppat.1014573.ref024","doi-asserted-by":"crossref","DOI":"10.1128\/jvi.00932-24","article-title":"Advances in African swine fever virus molecular biology and host interactions contributing to new tools for control","volume":"99","author":"LK 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