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      M448R and MGF505-7R: Two African Swine Fever Virus Antigens Commonly Recognized by ASFV-Specific T-Cells and with Protective Potential

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          Abstract

          African swine fever (ASF) is today′s number one threat for the global swine industry. Neither commercial vaccine nor treatment is available against ASF and, thus far, only live attenuated viruses (LAV) have provided robust protection against lethal ASF virus (ASFV) challenge infections. Identification of ASFV proteins inducing protective immune responses is one of the major challenges to develop safer and efficient subunit vaccines. Immunopeptidomic studies recently performed in our laboratory allowed identifying ASFV antigens recognized by ASFV-specific CD8 + T-cells. Here, we used data from the SLAI-peptide repertoire presented by a single set of ASFV-infected porcine alveolar macrophages to generate a complex DNA vaccine composed by 15 plasmids encoding the individual peptide-bearing ORFs. DNA vaccine priming improved the protection afforded by a suboptimal dose of the BA71ΔCD2 LAV given as booster vaccination, against Georgia2007/1 lethal challenge. Interestingly, M448R was the only protein promiscuously recognized by the induced ASFV-specific T-cells. Furthermore, priming pigs with DNA plasmids encoding M488R and MGF505-7R, a CD8 + T-cell antigen previously described, confirmed these two proteins as T-cell antigens with protective potential. These studies might be useful to pave the road for designing safe and more efficient vaccine formulations in the future.

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            Evolutionary genomics of nucleo-cytoplasmic large DNA viruses.

            A previous comparative-genomic study of large nuclear and cytoplasmic DNA viruses (NCLDVs) of eukaryotes revealed the monophyletic origin of four viral families: poxviruses, asfarviruses, iridoviruses, and phycodnaviruses [Iyer, L.M., Aravind, L., Koonin, E.V., 2001. Common origin of four diverse families of large eukaryotic DNA viruses. J. Virol. 75 (23), 11720-11734]. Here we update this analysis by including the recently sequenced giant genome of the mimiviruses and several additional genomes of iridoviruses, phycodnaviruses, and poxviruses. The parsimonious reconstruction of the gene complement of the ancestral NCLDV shows that it was a complex virus with at least 41 genes that encoded the replication machinery, up to four RNA polymerase subunits, at least three transcription factors, capping and polyadenylation enzymes, the DNA packaging apparatus, and structural components of an icosahedral capsid and the viral membrane. The phylogeny of the NCLDVs is reconstructed by cladistic analysis of the viral gene complements, and it is shown that the two principal lineages of NCLDVs are comprised of poxviruses grouped with asfarviruses and iridoviruses grouped with phycodnaviruses-mimiviruses. The phycodna-mimivirus grouping was strongly supported by several derived shared characters, which seemed to rule out the previously suggested basal position of the mimivirus [Raoult, D., Audic, S., Robert, C., Abergel, C., Renesto, P., Ogata, H., La Scola, B., Suzan, M., Claverie, J.M. 2004. The 1.2-megabase genome sequence of Mimivirus. Science 306 (5700), 1344-1350]. These results indicate that the divergence of the major NCLDV families occurred at an early stage of evolution, prior to the divergence of the major eukaryotic lineages. It is shown that subsequent evolution of the NCLDV genomes involved lineage-specific expansion of paralogous gene families and acquisition of numerous genes via horizontal gene transfer from the eukaryotic hosts, other viruses, and bacteria (primarily, endosymbionts and parasites). Amongst the expansions, there are multiple families of predicted virus-specific signaling and regulatory domains. Most NCLDVs have also acquired large arrays of genes related to ubiquitin signaling, and the animal viruses in particular have independently evolved several defenses against apoptosis and immune response, including growth factors and potential inhibitors of cytokine signaling. The mimivirus displays an enormous array of genes of bacterial provenance, including a representative of a new class of predicted papain-like peptidases. It is further demonstrated that a significant number of genes found in NCLDVs also have homologs in bacteriophages, although a vertical relationship between the NCLDVs and a particular bacteriophage group could not be established. On the basis of these observations, two alternative scenarios for the origin of the NCLDVs and other groups of large DNA viruses of eukaryotes are considered. One of these scenarios posits an early assembly of an already large DNA virus precursor from which various large DNA viruses diverged through an ongoing process of displacement of the original genes by xenologous or non-orthologous genes from various sources. The second scenario posits convergent emergence, on multiple occasions, of large DNA viruses from small plasmid-like precursors through independent accretion of similar sets of genes due to strong selective pressures imposed by their life cycles and hosts.
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              RStudio: Integrated Development for R

              (2020)
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Vaccines (Basel)
                Vaccines (Basel)
                vaccines
                Vaccines
                MDPI
                2076-393X
                14 May 2021
                May 2021
                : 9
                : 5
                : 508
                Affiliations
                [1 ]IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA), Campus de la Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain; laia.bosch@ 123456irta.cat (L.B.-C.); elisabeth.lopezf@ 123456gmail.com (E.L.); mariajesus.navas@ 123456irta.cat (M.J.N.); miguel.blanco@ 123456irta.cat (M.B.-F.); sonia.pina@ 123456irta.cat (S.P.-P.); francesc.accensi@ 123456irta.cat (F.A.)
                [2 ]OIE Collaborating Centre for the Research and Control of Emerging and Re-Emerging Swine Diseases in Europe (IRTA-CReSA), 08193 Bellaterra, Spain
                [3 ]Departament de Biologia Cellular, Fisiologia i Immunologia, Campus de la Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain; javiercolladomiguens@ 123456gmail.com
                [4 ]UAB, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain
                [5 ]Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autònoma de Madrid, 28049 Madrid, Spain; mlsalas@ 123456cbm.csic.es
                [6 ]Boehringer Ingelheim Veterinary Research Center (BIVRC) GmbH & Co. KG, 30559 Hannover, Germany; egbert.mundt@ 123456boehringer-ingelheim.com (E.M.); veljko.nikolin@ 123456boehringer-ingelheim.com (V.N.)
                Author notes
                Author information
                https://orcid.org/0000-0003-4253-330X
                https://orcid.org/0000-0002-8251-0682
                https://orcid.org/0000-0001-5475-4770
                https://orcid.org/0000-0001-9068-0377
                https://orcid.org/0000-0001-7361-8408
                Article
                vaccines-09-00508
                10.3390/vaccines9050508
                8156282
                34069239
                3c49d2bb-4e30-43a5-9349-7d57a88a803c
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 29 March 2021
                : 12 May 2021
                Categories
                Article

                african swine fever,antigen discovery,t-cells,dna immunization,live attenuated virus,protection,immunopeptidomics

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