{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T22:47:59Z","timestamp":1787698079565,"version":"build-2784847793"},"reference-count":64,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Development and Application of a Vaccine Targeting the VP8 Subunit of Porcine Group A Rotavirus and an Accompanying Antibody Detection Kit","award":["2026YD011"],"award-info":[{"award-number":["2026YD011"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Porcine group A rotavirus (PoRVA) is a significant cause of viral diarrhea in piglets, necessitating urgent global implementation of effective control strategies. This review assesses advancements in PoRVA in vitro cultivation and amplification, crucial for PoRVA vaccine development. Traditional PoRVA cultivation commonly employs primary porcine kidney cells or finite cell lines like MA-104, posing well-documented challenges in scalability, production cost, and their ability to recapitulate the natural intestinal microenvironment. Consequently, research has increasingly focused on adapting PoRVA to alternative systems, particularly immortalized porcine cell lines or physiologically relevant porcine intestinal organoids. This adaptation process, involving serial passaging, can induce genomic alterations and virulence attenuation in piglets, essential for generating live attenuated vaccine (LAV) candidates. Modern biotechnological tools, such as reverse genetics and synthetic genomics, have expedited the creation of recombinant PoRVA strains with defined antigenic profiles and enhanced in vitro growth characteristics. However, a significant concern regarding LAV candidates derived from cell culture adaptation is the risk of virulence reversion upon pig back-passage, necessitating thorough safety and genetic stability evaluations. Nevertheless, utilizing stable cell lines or organoid platforms presents a feasible and cost-effective approach for large-scale PoRVA vaccine production. Future research should focus on identifying vaccine candidates that provide broad protection and exceptional safety, with an emphasis on cross-protection against divergent epidemic genotypes, while ensuring the economic feasibility of innovative manufacturing approaches.<\/jats:p>","DOI":"10.3390\/v18070718","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:58:04Z","timestamp":1782799084000},"page":"718","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cell Culture Adaptation of Porcine Group A Rotavirus: Advances and Challenges for Vaccine Development"],"prefix":"10.3390","volume":"18","author":[{"given":"Zhen","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Tarim University, Alar 843300, China"},{"name":"Tarim Animal Husbandry Science and Technology Key Laboratory of Xinjiang Production and Construction Corps, Alar 843300, China"},{"name":"Tarim Animal Disease Diagnosis and Prevention Engineering Laboratory of Xinjiang Production and Construction Corps, Alar 843300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baihe","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Tarim University, Alar 843300, China"},{"name":"Tarim Animal Husbandry Science and Technology Key Laboratory of Xinjiang Production and Construction Corps, Alar 843300, China"},{"name":"Tarim Animal Disease Diagnosis and Prevention Engineering Laboratory of Xinjiang Production and Construction Corps, Alar 843300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhua","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Tarim University, Alar 843300, China"},{"name":"Tarim Animal Husbandry Science and Technology Key Laboratory of Xinjiang Production and Construction Corps, Alar 843300, China"},{"name":"Tarim Animal Disease Diagnosis and Prevention Engineering Laboratory of Xinjiang Production and Construction Corps, Alar 843300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Tarim University, Alar 843300, China"},{"name":"Tarim Animal Husbandry Science and Technology Key Laboratory of Xinjiang Production and Construction Corps, Alar 843300, China"},{"name":"Tarim Animal Disease Diagnosis and Prevention Engineering Laboratory of Xinjiang Production and Construction Corps, Alar 843300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiliang","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Tarim University, Alar 843300, China"},{"name":"Tarim Animal Husbandry Science and Technology Key Laboratory of Xinjiang Production and Construction Corps, Alar 843300, China"},{"name":"Tarim Animal Disease Diagnosis and Prevention Engineering Laboratory of Xinjiang Production and Construction Corps, Alar 843300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanxin","family":"Liang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Tarim University, Alar 843300, China"},{"name":"Tarim Animal Husbandry Science and Technology Key Laboratory of Xinjiang Production and Construction Corps, Alar 843300, China"},{"name":"Tarim Animal Disease Diagnosis and Prevention Engineering Laboratory of Xinjiang Production and Construction Corps, Alar 843300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianrui","family":"Li","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Tarim University, Alar 843300, China"},{"name":"Tarim Animal Husbandry Science and Technology Key Laboratory of Xinjiang Production and Construction Corps, Alar 843300, China"},{"name":"Tarim Animal Disease Diagnosis and Prevention Engineering Laboratory of Xinjiang Production and Construction Corps, Alar 843300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1128\/CDLI.8.1.129-132.2001","article-title":"Genomic characterization of porcine rotaviruses in Italy","volume":"8","author":"Martella","year":"2001","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/avj.13229","article-title":"Detection and genetic diversity of porcine rotavirus A, B and C in eastern Australian piggeries","volume":"101","author":"Genz","year":"2023","journal-title":"Aust. Vet. J."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Monteagudo, L.V., Benito, A.A., L\u00e1zaro-Gaspar, S., Arnal, J.L., Martin-Jurado, D., Menjon, R., and Qu\u00edlez, J. (2022). Occurrence of Rotavirus A Genotypes and Other Enteric Pathogens in Diarrheic Suckling Piglets from Spanish Swine Farms. Animals, 12.","DOI":"10.3390\/ani12030251"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13567-018-0619-6","article-title":"Development of a live attenuated trivalent porcine rotavirus A vaccine against disease caused by recent strains most prevalent in South Korea","volume":"50","author":"Park","year":"2019","journal-title":"Vet. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"veag013","DOI":"10.1093\/ve\/veag013","article-title":"Genetic and antigenic diversity of rotavirus A in faeces from Danish pigs","volume":"12","author":"Pedersen","year":"2026","journal-title":"Virus Evol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1128\/jcm.26.7.1277-1282.1988","article-title":"Serial propagation of porcine group C rotavirus (pararotavirus) in a continuous cell line and characterization of the passaged virus","volume":"26","author":"Saif","year":"1988","journal-title":"J. Clin. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.jviromet.2015.07.016","article-title":"Isolation and propagation of the animal rotaviruses in MA-104 cells--30 years of practical experience","volume":"223","author":"Otto","year":"2015","journal-title":"J. Virol. Methods"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s00418-005-0067-z","article-title":"Characterization of a porcine intestinal epithelial cell line for in vitro studies of microbial pathogenesis in swine","volume":"125","author":"Schierack","year":"2006","journal-title":"Histochem. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Guo, Y., Candelero-Rueda, R.A., Saif, L.J., and Vlasova, A.N. (2021). Infection of porcine small intestinal enteroids with human and pig rotavirus A strains reveals contrasting roles for histo-blood group antigens and terminal sialic acids. PLoS Pathog., 17.","DOI":"10.1371\/journal.ppat.1009237"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"110036","DOI":"10.1016\/j.vetmic.2024.110036","article-title":"Rotavirus infection inhibits SLA-I expression on the cell surface by degrading \u03b22 M via ERAD-proteasome pathway","volume":"292","author":"Jing","year":"2024","journal-title":"Vet. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Snyder, A.J., Agbemabiese, C.A., and Patton, J.T. (2024). Production of OSU G5P[7] Porcine Rotavirus Expressing a Fluorescent Reporter via Reverse Genetics. Viruses, 16.","DOI":"10.1101\/2024.01.26.577454"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Liu, C., Wei, H., Zhang, X., Wu, W., Shen, Z., Luo, F., and Deng, S. (2025). Establishment of a reverse genetics system for an epidemic strain of porcine rotavirus JXAY01 type G5P[23]I12. Front. Vet. Sci., 11.","DOI":"10.3389\/fvets.2024.1512327"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"15195","DOI":"10.1038\/s41598-018-33305-1","article-title":"Establishment of porcine enterocyte\/myofibroblast co-cultures for the growth of porcine rota- and coronaviruses","volume":"8","author":"Cui","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1002\/biot.201400388","article-title":"Designing cell lines for viral vaccine production: Where do we stand?","volume":"10","author":"Genzel","year":"2015","journal-title":"Biotechnol. J."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Iaconis, G., Jackson, B., Childs, K., Boyce, M., Goodbourn, S., Blake, N., Iturriza-Gomara, M., and Seago, J. (2021). Rotavirus NSP1 Inhibits Type I and Type III Interferon Induction. Viruses, 13.","DOI":"10.3390\/v13040589"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Deb, R., Yadav, A.K., Rajkhowa, S., and Malik, Y.S. (2022). Cell Culture System for Porcine Virus Isolation and Propagation. Protocols for the Diagnosis of Pig Viral Diseases, Springer Nature Humana Press. Springer Protocols Handbooks.","DOI":"10.1007\/978-1-0716-2043-4"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"de Sautu, M., Leistner, C., Kirchhausen, T., Jenni, S., and Harrison, S.C. (2026). Mechanism of membrane perforation in rotavirus cell entry. bioRxiv.","DOI":"10.64898\/2026.01.21.700916"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41541-024-01007-7","article-title":"CRISPR\/Cas9 screens identify key host factors that enhance rotavirus reverse genetics efficacy and vaccine production","volume":"9","author":"Zhu","year":"2024","journal-title":"npj Vaccines"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wang, Z., Huang, W., Yan, G., Tian, Y., Wang, C., Mao, X., Sun, M., Zhou, L., Yu, C., and Xia, H. (2025). Isolation, Genomic Characterization, and Immunogenicity Evaluation of a G9P[23] Porcine Rotavirus Strain. Vet. Sci., 12.","DOI":"10.3390\/vetsci12020180"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Guo, Y., Wentworth, D.E., Stucker, K.M., Halpin, R.A., Lam, H.C., Marthaler, D., Saif, L.J., and Vlasova, A.N. (2020). Amino Acid Substitutions in Positions 385 and 393 of the Hydrophobic Region of VP4 May Be Associated with Rotavirus Attenuation and Cell Culture Adaptation. Viruses, 12.","DOI":"10.3390\/v12040408"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e00889-20","DOI":"10.1128\/JVI.00889-20","article-title":"Serial Passaging of the Human Rotavirus CDC-9 Strain in Cell Culture Leads to Attenuation: Characterization from In Vitro and In Vivo Studies","volume":"94","author":"Resch","year":"2020","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1128\/JVI.76.3.1109-1123.2002","article-title":"VLA-2 (\u03b12\u03b21) integrin promotes rotavirus entry into cells but is not necessary for rotavirus attachment","volume":"76","author":"Ciarlet","year":"2002","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Wang, J., Qin, S., Li, K., Yin, X., Sun, D., and Chang, J. (2025). Rotavirus Reverse Genetics Systems and Oral Vaccine Delivery Vectors for Mucosal Vaccination. Microorganisms, 13.","DOI":"10.3390\/microorganisms13071579"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e0106725","DOI":"10.1128\/jvi.01067-25","article-title":"Mutations of two amino acids in VP5 mediate the attenuation of human rotavirus vaccine: Evidence from in vitro and in vivo studies","volume":"99","author":"Bessey","year":"2025","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Moiseenko, D., Chernyshev, R., Kamalova, N., Gavrilova, V., and Igolkin, A. (2025). Evolution of Porcine Virus Isolation: Guidelines for Practical Laboratory Application. Microorganisms, 13.","DOI":"10.3390\/microorganisms13122658"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1007\/978-1-4615-5331-1_91","article-title":"Adaptation and serial passage of bovine coronavirus in an established diploid swine testicular cell line and subsequent development of a modified live vaccine","volume":"440","author":"Welter","year":"1998","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Diep, N.V., Hayakawa-Sugaya, Y., Ishikawa, S., Kawaguchi, H., Suda, Y., Esaki, M., Okuya, K., and Ozawa, M. (2024). Establishment of an Immortalized Porcine Alveolar Macrophage Cell Line That Supports Efficient Replication of Porcine Reproductive and Respiratory Syndrome Viruses. Pathogens, 13.","DOI":"10.3390\/pathogens13121026"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1080\/22221751.2020.1772675","article-title":"A porcine macrophage cell line that supports high levels of replication of OURT88\/3, an attenuated strain of African swine fever virus","volume":"9","author":"Portugal","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4759","DOI":"10.1038\/s41598-021-84237-2","article-title":"An immortalized porcine macrophage cell line competent for the isolation of African swine fever virus","volume":"11","author":"Masujin","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Nelsen, A., Lager, K.M., Stasko, J., Nelson, E., Lin, C.M., and Hause, B.M. (2022). Identification of Pulmonary Infections with Porcine Rotavirus A in Pigs with Respiratory Disease. Front. Vet. Sci., 9.","DOI":"10.3389\/fvets.2022.918736"},{"key":"ref_31","first-page":"273","article-title":"Vaccine cell substrates: Bovine and porcine virus considerations","volume":"123","author":"Wessman","year":"2006","journal-title":"Dev. Biol."},{"key":"ref_32","first-page":"426","article-title":"Testing considerations for novel cell substrates: A regulatory perspective","volume":"64","author":"Khan","year":"2010","journal-title":"PDA J. Pharm. Sci. Technol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Meloni, D., Franzoni, G., and Oggiano, A. (2022). Cell Lines for the Development of African Swine Fever Virus Vaccine Candidates: An Update. Vaccines, 10.","DOI":"10.3390\/vaccines10050707"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/BF01311081","article-title":"Studies on attenuation of rotavirus. A comparison in piglets between virulent virus and its attenuated derivative","volume":"109","author":"Tzipori","year":"1989","journal-title":"Arch. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/BF01317601","article-title":"Synthesis of coreless, probably defective virus particles in cell cultures infected with rotaviruses","volume":"58","author":"McNulty","year":"1978","journal-title":"Arch. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1089\/vim.2009.0088","article-title":"Porcine small intestinal epithelial cell line [IPEC-J2] of rotavirus infection as a new model for the study of innate immune responses to rotaviruses and probiotics","volume":"23","author":"Liu","year":"2010","journal-title":"Viral Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1292\/jvms.17-0657","article-title":"The dynamics of a Chinese porcine G9P[23] rotavirus production in MA-104 cells and intestines of 3-day-old piglets","volume":"80","author":"Wang","year":"2018","journal-title":"J. Vet. Med. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Carter, M.H., Gribble, J., Diller, J.R., Denison, M.R., Mirza, S.A., Chappell, J.D., Halasa, N.B., and Ogden, K.M. (2024). Human Rotaviruses of Multiple Genotypes Acquire Conserved VP4 Mutations during Serial Passage. Viruses, 16.","DOI":"10.3390\/v16060978"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1007\/s00705-022-05510-x","article-title":"Effect of probiotic bacteria on porcine rotavirus OSU infection of porcine intestinal epithelial IPEC-J2 cells","volume":"167","author":"Leblanc","year":"2022","journal-title":"Arch. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6073","DOI":"10.1128\/JVI.00121-08","article-title":"Porcine rotavirus bearing an aberrant gene stemming from an intergenic recombination of the NSP2 and NSP5 genes is defective and interfering","volume":"82","author":"Cao","year":"2008","journal-title":"J. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/mi.2014.114","article-title":"Correlates of protection against human rotavirus disease and the factors influencing protection in low-income settings","volume":"8","author":"Clarke","year":"2015","journal-title":"Mucosal Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Takenouchi, T., Masujin, K., Miyazaki, A., Suzuki, S., Takagi, M., Kokuho, T., and Uenishi, H. (2022). Isolation and immortalization of macrophages derived from fetal porcine small intestine and their susceptibility to porcine viral pathogen infections. Front. Vet. Sci., 9.","DOI":"10.3389\/fvets.2022.919077"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1006\/mpat.1997.0198","article-title":"Rotavirus-specific proteins are detected in murine macrophages in both intestinal and extraintestinal lymphoid tissues","volume":"24","author":"Brown","year":"1998","journal-title":"Microb. Pathog."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s13567-018-0590-2","article-title":"Analysis of peptide-SLA binding by establishing immortalized porcine alveolar macrophage cells with different SLA class II haplotypes","volume":"49","author":"Le","year":"2018","journal-title":"Vet. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e0201525","DOI":"10.1128\/jvi.02015-25","article-title":"Simultaneous expression of three G genotypes of VP7 proteins in a recombinant porcine rotavirus confers protective immunity against multiple rotavirus infections","volume":"100","author":"Cheng","year":"2026","journal-title":"J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Rai, A., Pruitt, S., Ramirez-Medina, E., Vuono, E.A., Silva, E., Velazquez-Salinas, L., Carrillo, C., Borca, M.V., and Gladue, D.P. (2020). Identification of a Continuously Stable and Commercially Available Cell Line for the Identification of Infectious African Swine Fever Virus in Clinical Samples. Viruses, 12.","DOI":"10.3390\/v12080820"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Vlasova, A.N., Amimo, J.O., and Saif, L.J. (2017). Porcine Rotaviruses: Epidemiology, Immune Responses and Control Strategies. Viruses, 9.","DOI":"10.3390\/v9030048"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.meegid.2016.08.015","article-title":"Genomic changes detected after serial passages in cell culture of virulent human G1P[8] rotaviruses","volume":"45","author":"Tsugawa","year":"2016","journal-title":"Infect. Genet. Evol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5543","DOI":"10.1128\/JVI.00041-14","article-title":"Virulence-associated genome mutations of murine rotavirus identified by alternating serial passages in mice and cell cultures","volume":"88","author":"Tsugawa","year":"2014","journal-title":"J. Virol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1128\/JVI.01930-15","article-title":"Human Intestinal Enteroids: A New Model To Study Human Rotavirus Infection, Host Restriction, and Pathophysiology","volume":"90","author":"Saxena","year":"2015","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Gao, L., Shen, H., Zhao, S., Chen, S., Zhu, P., Lin, W., and Chen, F. (2023). Isolation and Pathogenicity Analysis of a G5P[23] Porcine Rotavirus Strain. Viruses, 16.","DOI":"10.20944\/preprints202311.0241.v1"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3322","DOI":"10.1016\/j.vaccine.2008.03.085","article-title":"Virus-specific intestinal IFN-gamma producing T cell responses induced by human rotavirus infection and vaccines are correlated with protection against rotavirus diarrhea in gnotobiotic pigs","volume":"26","author":"Yuan","year":"2008","journal-title":"Vaccine"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e01374-20","DOI":"10.1128\/JVI.01374-20","article-title":"Reverse Genetics Approach for Developing Rotavirus Vaccine Candidates Carrying VP4 and VP7 Genes Cloned from Clinical Isolates of Human Rotavirus","volume":"95","author":"Kanai","year":"2020","journal-title":"J. Virol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Falkenhagen, A., Patzina-Mehling, C., Gadicherla, A.K., Strydom, A., O\u2019Neill, H.G., and Johne, R. (2020). Generation of Simian Rotavirus Reassortants with VP4- and VP7-Encoding Genome Segments from Human Strains Circulating in Africa Using Reverse Genetics. Viruses, 12.","DOI":"10.3390\/v12020201"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e0062722","DOI":"10.1128\/jvi.00627-22","article-title":"Rotavirus VP4 Epitope of a Broadly Neutralizing Human Antibody Defined by Its Structure Bound with an Attenuated-Strain Virion","volume":"96","author":"Jenni","year":"2022","journal-title":"J. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Zhang, H., Zhao, H., Zhao, Y., Sui, L., Li, F., Zhang, H., Li, J., Jiang, Y., Cui, W., and Ding, G. (2022). Auxotrophic Lactobacillus Expressing Porcine Rotavirus VP4 Constructed Using CRISPR-Cas9D10A System Induces Effective Immunity in Mice. Vaccines, 10.","DOI":"10.3390\/vaccines10091510"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Guo, Y., Raev, S., Kick, M.K., Raque, M., Saif, L.J., and Vlasova, A.N. (2022). Rotavirus C Replication in Porcine Intestinal Enteroids Reveals Roles for Cellular Cholesterol and Sialic Acids. Viruses, 14.","DOI":"10.3390\/v14081825"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Ma, P., Fang, P., Ren, T., Fang, L., and Xiao, S. (2022). Porcine Intestinal Organoids: Overview of the State of the Art. Viruses, 14.","DOI":"10.3390\/v14051110"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2239937","DOI":"10.1080\/22221751.2023.2239937","article-title":"Infection of porcine enteroids and 2D differentiated intestinal epithelial cells with rotavirus A to study cell tropism and polarized immune response","volume":"12","author":"Yan","year":"2023","journal-title":"Emerg. Microbes Infect."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5114","DOI":"10.1016\/j.vaccine.2022.06.082","article-title":"Rotavirus vaccine-derived cases in Belgium: Evidence for reversion of attenuating mutations and alternative causes of gastroenteritis","volume":"40","author":"Simsek","year":"2022","journal-title":"Vaccine"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Maringa, W.M., Simwaka, J., Mwangi, P.N., Mpabalwani, E.M., Mwenda, J.M., Mphahlele, M.J., Seheri, M.L., and Nyaga, M.M. (2021). Whole Genome Analysis of Human Rotaviruses Reveals Single Gene Reassortant Rotavirus Strains in Zambia. Viruses, 13.","DOI":"10.3390\/v13091872"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"0871","DOI":"10.34133\/research.0871","article-title":"General Intelligence Framework to Predict Virus Adaptation Based on a Genome Language Model","volume":"8","author":"Jiang","year":"2025","journal-title":"Research"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e0155425","DOI":"10.1128\/jvi.01554-25","article-title":"Charting the virosphere: Computational synergies of AI and bioinformatics in viral discovery and evolution","volume":"99","author":"Sinno","year":"2025","journal-title":"J. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1097\/INF.0b013e31825d611e","article-title":"Vaccine-derived human-bovine double reassortant rotavirus in infants with acute gastroenteritis","volume":"31","author":"Hemming","year":"2012","journal-title":"Pediatr. Infect. Dis. 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