Cover of Journal of Virology: Viral disease advances in immune function and structure of African swine fever T-cell epitopes

Pork is an important source of protein for human intake, accounting for more than one-third of global meat production
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However, the outbreak of African Swine Fever (ASF) has a huge impact on the health of the pig herd and the stability of the industry
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The African swine fever virus (ASFV) that causes the disease was first identified in Kenya in 1921
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The African swine fever virus was first discovered in China in August 2018
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According to the World Organization for Animal Health (OIE) data, acute ASF can cause hemorrhage and high fever in pigs, and the mortality rate can be as high as 100%
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At present, it has been found in some animal experimental studies that although recombinant expressed protein vaccines designed based on structural proteins can induce corresponding neutralizing antibodies and delay clinical symptoms, neutralizing antibodies cannot provide sufficient protection, and pigs will still suffer from severe disease.
symptoms
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T cells are one of the main ways for the host to clear the virus, and studies have shown that T cells play an important role in the antiviral immunity and protection of ASFV
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Recently, Liu Jun, a researcher and collaborators from the Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, published a cover article entitled "Mooring stone-like Arg114 pullsdiverse bulged peptides: first insight into African swine fever virus" in the Journal of Virology.
-derived Tcell epitopes presented by swine MHC class I", by studying the function and structure of porcine leukocyte antigen type I SLA-1*0101, a common porcine leukocyte antigen in lean pigs.
The molecular mechanism of T cell recognition and presentation reveals that Arg114 of SLA-1*0101 has a peptide stabilization method similar to the "shipping stone", which is of great significance for the development and prevention of ASFV vaccines
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The study found that the motif of SLA-1*0101 binding polypeptide is different from that of most other mammalian MHC I molecules
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Other MHC I molecules use the P2 (peptide 2) and PΩ (polypeptide C-terminal) amino acids of the peptide as the main anchor residues, while the peptide bound by SLA-1*0101 uses P3 and PΩ as the main anchor residues, And there is a strong preference for negatively charged amino acids at positions P3-P7
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Figure 1 The unique motif of SLA-1*0101-binding peptide In the peptide binding groove (PBG), the conformationally stable positively charged amino acid Arg114 plays an important role in the selection of peptide binding
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Arg114 has a preference for the negatively charged amino acids in the P5-P7 position of the polypeptide.
When the negatively charged amino acid appears in the middle of the polypeptide, the Arg114 residue acts as a "mooring stone" to "tether" the polypeptide to the PBG of SLA-1*0101
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At the same time, because of whether the middle position of the peptide is negatively charged and the difference in the negatively charged position, the peptide also exhibits a variety of different convex conformational changes.

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The existence of these multiple patterns also predicts the diversity of SLA-1*0101-presented polypeptides recognized by T cell receptors
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Figure 2 The selection method of porcine MHC I molecule similar to the "mooring stone" formula and its effect on conformation Derivatized Peptides SLA-1*0101 tetramers were prepared for T cell recognition of the peptides by flow cytometry
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The results showed that peptide tetramers could detect different proportions of antigen-specific CD8+ T cells in PBMCs of donor pigs (Fig.
4)
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The related peptides can stimulate strong T-cell immunity in the widely distributed SLA-1*0101 gender pig herd, which provides a new idea for the development of ASFV vaccines
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Fig.
3 Recognition of the functional epitope of ASFV by T cellsFig.
4 Cover image of Journal of Virology, Issue 4, 2022 More precise screening of new T-cell immunogens provides new insights into ASFV vaccine development
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Academician Gao Fu and researcher Liu Jun of the Institute for Viral Disease Control and Prevention of the Chinese Center for Disease Control and Prevention, and Professor Gao Guolan of the University of Science of China are the co-corresponding authors of the paper
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Yue Can, a doctoral student at the University of Science of China, Xiang Wang Zhen from the China Animal Husbandry Research Institute, Huang Xiaowen, a master student at the University of Science of China, and Sun Yuan, a researcher from the Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, are the co-first authors of the paper
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This research was supported by the National Key Research and Development Program, the National Natural Science Foundation of China and other projects
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This study was strongly supported by Qiu Huaji, a researcher from the Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Xiao Jin, a researcher from the China Animal Husbandry Research Institute, Qi Jianxun, a researcher from the Institute of Microbiology, Chinese Academy of Sciences, and Sun Zeyu, a researcher from the First Affiliated Hospital of Zhejiang University School of Medicine.
Supported by the National Key R&D Program, National Natural Science Foundation of China and other projects
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In recent years, researcher Liu Jun from the Institute of Viral Diseases of the Chinese Center for Disease Control and Prevention has carried out a series of research work on the cellular immune response mechanism of influenza and other viruses (including Immunity, 9 articles by J Virol, 7 articles by J Immunol, etc.
) It is a cellular immune detection platform for an important experimental animal, systematically expounds the molecular mechanism of the presentation of different viral epitopes and their T cell recognition by multiple species, and provides new ideas and scientific basis for the prevention and control of emerging and recurrent viral diseases
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Paper link: https://doi.
org/10.
1128/jvi.
01378-21