biostudies-literatureZhang HNational Natural Science Foundation of ChinaKey Rearch Program of Frontier Sciences of the Chinese Academy of Sciencese0116722https://www.ebi.ac.uk/biostudies/studies/S-EPMC9769380biostudies-literatureUnknown96(24)The correct formation of native disulfide bonds is critical for the proper structure and function of many proteins. Cellular disulfide bond formation pathways commonly consist of two parts: sulfhydryl oxidase-mediated oxidation and disulfide isomerase-mediated isomerization. Some large DNA viruses, such as baculoviruses, encode sulfhydryl oxidases, but viral disulfide isomerases have not yet been identified, although G4L in poxvirus has been suggested to serve such a function. Here, we report that the baculovirus core gene <i>ac81</i> encodes a putative disulfide isomerase. <i>ac81</i> is conserved in baculoviruses, nudiviruses, and hytrosaviruses. We found that AC81 homologs contain a typical thioredoxin fold conserved in disulfide isomerases. To determine the role of AC81, a series of AuJournal of virologyAC81 Is a Putative Disulfide Isomerase Involved in Baculoviral Disulfide Bond Formation.PMC97693803220012631570153QYZDJ-SSW-SMC021Wang MKuang WFu CLi JHu ZZhang HfalseAC81 Is a Putative Disulfide Isomerase Involved in Baculoviral Disulfide Bond Formation.The correct formation of native disulfide bonds is critical for the proper structure and function of many proteins. Cellular disulfide bond formation pathways commonly consist of two parts: sulfhydryl oxidase-mediated oxidation and disulfide isomerase-mediated isomerization. Some large DNA viruses, such as baculoviruses, encode sulfhydryl oxidases, but viral disulfide isomerases have not yet been identified, although G4L in poxvirus has been suggested to serve such a function. Here, we report that the baculovirus core gene <i>ac81</i> encodes a putative disulfide isomerase. <i>ac81</i> is conserved in baculoviruses, nudiviruses, and hytrosaviruses. We found that AC81 homologs contain a typical thioredoxin fold conserved in disulfide isomerases. To determine the role of AC81, a series of Au2022-01-01T00:00:00Z2022 Dec2025-04-22T04:56:46.806Z2025-04-05T21:07:00.97ZS-EPMC97693803646886110.1128/jvi.01167-22