{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:23:36Z","timestamp":1788269016554,"version":"build-2803163510"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32172818"],"award-info":[{"award-number":["32172818"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Special Program on Science and Technology Innovation Capacity Building of BAAFS","award":["KJCX20230424"],"award-info":[{"award-number":["KJCX20230424"]}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["6232012"],"award-info":[{"award-number":["6232012"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFD1301003"],"award-info":[{"award-number":["2024YFD1301003"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Beijing Innovation Team of Technology Systems in the Dairy Industry","award":["BAIC06-2025"],"award-info":[{"award-number":["BAIC06-2025"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Although bovine herpesvirus 1 (BoHV-1) causes massive losses of cattle, the transition from mucosal replication to neuroinvasion remains poorly understood. Using a controlled calf model, we integrated quantitative virology and transcriptomics to map its pathogenesis and define the role of promyelocytic leukemia protein (PML). Calves inoculated intranasally and ocularly (1.4 \u00d7 10\n                      <jats:sup>6<\/jats:sup>\n                      plaque-forming units\/head) were sampled daily (1\u201314 days post-infection, dpi) for glycoprotein B (gB) qPCR. Tissues were analyzed at 4 and 14 dpi to measure viral DNA via gB-specific qPCR, and for mRNA-seq of trigeminal ganglia (TG). Shedding peaked at 3\u20136 dpi, being highest in nasal samples, lower in ocular samples, and substantially lower in rectal samples, and declined by 10\u201314 dpi. At 4 dpi, among the tissues sampled, the tonsils exhibited the highest viral burden. TG exhibited low viral levels at 4 dpi, although they remained detectable at 14 dpi, indicating neuroinvasion. The TG program shifted from early proteostasis priming (4 dpi) to immune\/extracellular matrix activation with synaptic repression (14 dpi). In MDBK\/Vero cells, IFN-\u03b1 resulted in higher bovine PML (bPML) levels and enlarged PML nuclear bodies (PML-NBs), reducing very early viral DNA levels, whereas BoHV-1 disrupted PML-NB integrity. The different bPML isoforms exerted different effects on viral infection. STRING analysis revealed a conserved PML\u2013SUMO1\u2013UBE2I\u2013DAXX\u2013SP100 core. These findings delineate the mucosal-to-neuronal trajectory, establish PML as both an effector and viral target in complementary\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      systems, and identify SUMO\/ubiquitin-linked proteostasis as a tractable target for antiviral intervention.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>Although bovine herpesvirus 1 (BoHV-1) remains a major challenge to cattle health, the early transition from mucosal replication to trigeminal neuroinvasion has not been clearly mapped in natural-host calves. By integrating daily shedding kinetics, tissue viral DNA profiling, and time-resolved trigeminal ganglion transcriptomics, we delineate when and how BoHV-1 reaches the sensory neurons. Promyelocytic leukemia protein (PML) is identified as a key intrinsic antiviral factor that is upregulated by IFN-\u03b1 and restricts very early viral genome accumulation, while viral BoHV-1-encoded infected cell protein 0 actively dismantles PML nuclear bodies. The discovery of opposing isoform-specific PML functions and a conserved PML\u2013SUMO proteostasis hub provides mechanistic insight into BoHV-1 immune evasion. These findings refine our understanding of the mucosal-to-neuronal trajectory of infection and highlight proteostasis-linked antiviral pathways as promising targets for intervention.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.02698-25","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T13:01:06Z","timestamp":1784811666000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Time-resolved mapping in calves reveals bovine herpesvirus 1 shift from mucosal replication to trigeminal ganglion neuroinvasion with promyelocytic leukemia protein-centered host\u2013virus antagonism"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5927-372X","authenticated-orcid":false,"given":"Yong","family":"Wang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04trzn023","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences","place":["Beijing, China"]},{"name":"Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry","place":["Beijing, China"]},{"name":"Sino-UK Joint Laboratory for Prevention & Control of Infectious Diseases in Livestock and Poultry","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Jin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04trzn023","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of 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Poultry","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyao","family":"Cao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04trzn023","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences","place":["Beijing, China"]},{"name":"Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry","place":["Beijing, China"]},{"name":"Sino-UK Joint Laboratory for Prevention & Control of Infectious Diseases in Livestock and Poultry","place":["Beijing, China"]},{"name":"Xiangcheng Municipal Bureau of Agriculture and Rural Affairs","place":["Henan Province, 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