Citation: Linlin Zhang, Yali Duan, Wei Wang, Qi Li, Jiao Tian, Yun Zhu, Ran Wang, Zhengde Xie. Autophagy induced by human adenovirus B7 structural protein VI inhibits viral replication .VIROLOGICA SINICA, 2023, 38(5) : 709-722.  http://dx.doi.org/10.1016/j.virs.2023.08.002

Autophagy induced by human adenovirus B7 structural protein VI inhibits viral replication

  • Corresponding author: Zhengde Xie, xiezhengde@bch.com.cn
  • Received Date: 09 February 2023
    Accepted Date: 31 July 2023
    Available online: 05 August 2023
  • Human adenovirus B7 (HAdV-B7) causes severe acute lower respiratory tract infections in children. However, neither the child-specific antivirals or vaccines are available, nor the pathogenesis is clear. Autophagy, as part of innate immunity, plays an important role in resistance to viral infection by degrading the virus and promoting the development of innate and adaptive immunity. This study provided evidence that HAdV-B7 infection induced complete autophagic flux, and the pharmacological induction of autophagy decreased HAdV-B7 replication. In this process, the host protein Bcl2-associated athanogene 3 (BAG3) mediated autophagy to inhibit the replication of HAdV-B7 by binding to the PPSY structural domain of viral protein pVI through its WW structural domain. These findings further our understanding of the host immune response during viral infection and will help to develop broad anti-HAdV therapies.

  • 加载中
  • 10.1016j.virs.2023.08.002-ESM3.xlsx
    10.1016j.virs.2023.08.002-ESM2.xlsx
    10.1016j.virs.2023.08.002-ESM1.docx
    1. Behl, C., 2016. Breaking BAG:The Co-Chaperone BAG3 in Health and Disease. Trends Pharmacol Sci, 37, 672-688.

    2. Chen, T., Tu, S., Ding, L., Jin, M., Chen, H.,Zhou, H., 2023. The role of autophagy in viral infections. J Biomed Sci, 30, 5.

    3. Choi, Y., Bowman, J.W.,Jung, J.U., 2018. Autophagy during viral infection-a double-edged sword. Nat Rev Microbiol, 16, 341-354.

    4. Daussy, C.F., Pied, N.,Wodrich, H., 2021. Understanding Post Entry Sorting of Adenovirus Capsids; A Chance to Change Vaccine Vector Properties. Viruses, 13:1221.

    5. Dikic, I.,Elazar, Z., 2018. Mechanism and medical implications of mammalian autophagy. Nat Rev Mol Cell Biol, 19, 349-364.

    6. Duan, Y., Li, C., Deng, L., An, S., Zhu, Y., Wang, W., Zhang, M., Xu, L., Xu, B., Chen, X.,Xie, Z., 2021. Genetic Analysis of Human Adenovirus Type 7 Strains Circulating in Different Parts of China. Virol Sin, 36, 382-392.

    7. Greber, U.F., 2020. Adenoviruses-Infection, pathogenesis and therapy. FEBS Lett, 594, 1818-1827.

    8. Han, Z., Sagum, C.A., Bedford, M.T., Sidhu, S.S., Sudol, M.,Harty, R.N., 2016. ITCH E3 Ubiquitin Ligase Interacts with Ebola Virus VP40 To Regulate Budding. J Virol, 90, 9163-9171.

    9. Huang, P.Q., Du, H., Chen, H.B., Li, Y., Chen, H.W., Lei, X.L., Zhang, M.R.,Lu, X.X., 2022. Invasive pulmonary fungal infections in children with severe human adenovirus type 7 pneumonia:A retrospective study. Pediatrics & Neonatology, 63, 388-393.

    10. Jiao, Y., Kong, N., Wang, H., Sun, D., Dong, S., Chen, X., Zheng, H., Tong, W., Yu, H., Yu, L., Huang, Y., Wang, H., Sui, B., Zhao, L., Liao, Y., Zhang, W., Tong, G.,Shan, T., 2021. PABPC4 Broadly Inhibits Coronavirus Replication by Degrading Nucleocapsid Protein through Selective Autophagy. Microbiol Spectr, 9, e0090821.

    11. Kim, S., Choi, S.,Kang, D., 2020. Quantitative and qualitative analysis of autophagy flux using imaging. BMB Rep, 53, 241-247.

    12. Klionsky, D.J., Abdel-Aziz, A.K., Abdelfatah, S., Brand-Saberi, B., Dong, X.C., Kenchappa, C.S., Li, Z., Lin, Y., Oshima, S., Rong, Y., Sluimer, J.C., Stallings, C.L.,Tong, C.K., 2021. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)(1). Autophagy, 17, 1-382.

    13. Kong, N., Shan, T., Wang, H., Jiao, Y., Zuo, Y., Li, L., Tong, W., Yu, L., Jiang, Y., Zhou, Y., Li, G., Gao, F., Yu, H., Zheng, H.,Tong, G., 2020. BST2 suppresses porcine epidemic diarrhea virus replication by targeting and degrading virus nucleocapsid protein with selective autophagy. Autophagy, 16, 1737-1752.

    14. Li, Y., Hu, B., Ji, G., Zhang, Y., Xu, C., Lei, J., Ding, C.,Zhou, J., 2020. Cytoplasmic Cargo Receptor p62 Inhibits Avibirnavirus Replication by Mediating Autophagic Degradation of Viral Protein VP2. J Virol, 94:e01255-20.

    15. Liang, J., Djurkovic, M.A., Shtanko, O.,Harty, R.N., 2023. Chaperone-assisted selective autophagy targets filovirus VP40 as a client and restricts egress of virus particles. Proc Natl Acad Sci U S A, 120, e2210690120.

    16. Liang, J., Sagum, C.A., Bedford, M.T., Sidhu, S.S., Sudol, M., Han, Z.,Harty, R.N., 2017. Chaperone-Mediated Autophagy Protein BAG3 Negatively Regulates Ebola and Marburg VP40-Mediated Egress. PLoS Pathog, 13, e1006132.

    17. Liu, W., Qiu, S., Zhang, L., Wu, H., Tian, X., Li, X., Xu, D., Dai, J., Gu, S., Liu, Q., Chen, D.,Zhou, R., 2022. Analysis of severe human adenovirus infection outbreak in Guangdong Province, southern China in 2019. Virol Sin, 37, 331-340.

    18. Liu, Y., Tang, Q., Rao, Z., Fang, Y., Jiang, X., Liu, W., Luan, F.,Zeng, N., 2021. Inhibition of herpes simplex virus 1 by cepharanthine via promoting cellular autophagy through up-regulation of STING/TBK1/P62 pathway. Antiviral Res, 193, 105143.

    19. Lu, G., Peng, X., Li, R., Liu, Y., Wu, Z., Wang, X., Zhang, D., Zhao, J., Sun, Y., Zhang, L., Yang, P.,Wang, Q., 2020. An outbreak of acute respiratory infection at a training base in Beijing, China due to human adenovirus type B55. BMC Infect Dis, 20, 537.

    20. Maier, O., Galan, D.L., Wodrich, H.,Wiethoff, C.M., 2010. An N-terminal domain of adenovirus protein VI fragments membranes by inducing positive membrane curvature. Virology, 402, 11-19.

    21. Maier, O., Marvin, S.A., Wodrich, H., Campbell, E.M.,Wiethoff, C.M., 2012. Spatiotemporal dynamics of adenovirus membrane rupture and endosomal escape. J Virol, 86, 10821-10828.

    22. Mcguire, K.A., Barlan, A.U., Griffin, T.M.,Wiethoff, C.M., 2011. Adenovirus type 5 rupture of lysosomes leads to cathepsin B-dependent mitochondrial stress and production of reactive oxygen species. J Virol, 85, 10806-10813.

    23. Montespan, C., Marvin, S.A., Austin, S., Burrage, A.M., Roger, B., Rayne, F., Faure, M., Campell, E.M., Schneider, C., Reimer, R., Grunewald, K., Wiethoff, C.M.,Wodrich, H., 2017a. Multi-layered control of Galectin-8 mediated autophagy during adenovirus cell entry through a conserved PPxY motif in the viral capsid. PLoS Pathog, 13, e1006217.

    24. Montespan, C., Wiethoff, C.M.,Wodrich, H., 2017b. A Small Viral PPxY Peptide Motif To Control Antiviral Autophagy. J Virol, 91:e00581-17.

    25. Mouna, L., Hernandez, E., Bonte, D., Brost, R., Amazit, L., Delgui, L.R., Brune, W., Geballe, A.P., Beau, I.,Esclatine, A., 2016. Analysis of the role of autophagy inhibition by two complementary human cytomegalovirus BECN1/Beclin 1-binding proteins. Autophagy, 12, 327-342.

    26. National Health Commission of the People's Republic of China, National Administration of Traditional Chinese Medicine, 2019. Guideline for diagnosis and treatment of adenovirus pneumonia in children (2019 version). Chin J Clin Infect Dis, 32:293-298. (In Chinese).

    27. Pied, N., Daussy, C.F., Denis, Z., Ragues, J., Faure, M., Iggo, R., Tschan, M.P., Roger, B., Rayne, F.,Wodrich, H., 2022. TBK1 is part of a galectin 8 dependent membrane damage recognition complex and drives autophagy upon Adenovirus endosomal escape. PLoS Pathog, 18, e1010736.

    28. Probst, V., Spieker, A.J., Stopczynski, T., Stewart, L.S., Haddadin, Z., Selvarangan, R., Harrison, C.J., Schuster, J.E., Staat, M.A., Mcneal, M., Weinberg, G.A., Szilagyi, P.G., Boom, J.A., Sahni, L.C., Piedra, P.A., Englund, J.A., Klein, E.J., Michaels, M.G., Williams, J.V., Campbell, A.P., Patel, M., Gerber, S.I.,Halasa, N.B., 2022. Clinical Presentation and Severity of Adenovirus Detection Alone vs Adenovirus Co-detection With Other Respiratory Viruses in US Children With Acute Respiratory Illness from 2016 to 2018. J Pediatric Infect Dis Soc, 11, 430-439.

    29. Reddy, V.S.,Barry, M.A., 2021. Structural Organization and Protein-Protein Interactions in Human Adenovirus Capsid. Subcell Biochem, 96, 503-518.

    30. Rosati, A., Khalili, K., Deshmane, S.L., Radhakrishnan, S., Pascale, M., Turco, M.C.,Marzullo, L., 2009. BAG3 protein regulates caspase-3 activation in HIV-1-infected human primary microglial cells. J Cell Physiol, 218, 264-267.

    31. Shen, C.F., Wang, S.M., Ho, T.S.,Liu, C.C., 2017. Clinical features of community acquired adenovirus pneumonia during the 2011 community outbreak in Southern Taiwan:role of host immune response. BMC Infect Dis, 17, 196.

    32. Sturner, E.,Behl, C., 2017. The Role of the Multifunctional BAG3 Protein in Cellular Protein Quality Control and in Disease. Front Mol Neurosci, 10, 177.

    33. Takayama, S.,Reed, J.C., 2001. Molecular chaperone targeting and regulation by BAG family proteins. Nat Cell Biol, 3, E237-241.

    34. Wo, Y., Lu, Q.B., Huang, D.D., Li, X.K., Guo, C.T., Wang, H.Y., Zhang, X.A., Liu, W.,Cao, W.C., 2015. Epidemical features of HAdV-3 and HAdV-7 in pediatric pneumonia in Chongqing, China. Arch Virol, 160, 633-638.

    35. Xu, C., Li, T., Lei, J., Zhang, Y., Zhou, J.,Hu, B., 2021. The Autophagy Cargo Receptor SQSTM1 Inhibits Infectious Bursal Disease Virus Infection through Selective Autophagic Degradation of Double-Stranded Viral RNA. Viruses, 13:2494.

    36. Yamamoto, H., Zhang, S.,Mizushima, N., 2023. Autophagy genes in biology and disease. Nat Rev Genet, 10.1038/s41576-022-00562-w, 1-19.

    37. Yoon, B.W., Song, Y.G.,Lee, S.H., 2017. Severe community-acquired adenovirus pneumonia treated with oral ribavirin:a case report. BMC Res Notes, 10, 47.

    38. Yu, P., Ma, C., Nawaz, M., Han, L., Zhang, J., Du, Q., Zhang, L., Feng, Q., Wang, J.,Xu, J., 2013. Outbreak of acute respiratory disease caused by human adenovirus type 7 in a military training camp in Shaanxi, China. Microbiology & Immunology, 57, 553-560.

    39. Zhang, N., Wang, L., Deng, X., Liang, R., Su, M., He, C., Hu, L., Su, Y., Ren, J., Yu, F., Du, L.,Jiang, S., 2020. Recent advances in the detection of respiratory virus infection in humans. J Med Virol, 92, 408-417.

  • 加载中

Article Metrics

Article views(1767) PDF downloads(17) Cited by()

Related
Proportional views

    Autophagy induced by human adenovirus B7 structural protein VI inhibits viral replication

      Corresponding author: Zhengde Xie, xiezhengde@bch.com.cn
    • a. Beijing Key Laboratory of Pediatric Respiratory Infectious Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, Laboratory of Infection and Virology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China;
    • b. Research Unit of Critical Infection in Children, 2019RU016, Chinese Academy of Medical Sciences, Beijing, 100045, China;
    • c. Department of Infectious Diseases, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China;
    • d. Beijing Coal Group General Hospital, Beijing, 100045, China

    Abstract: Human adenovirus B7 (HAdV-B7) causes severe acute lower respiratory tract infections in children. However, neither the child-specific antivirals or vaccines are available, nor the pathogenesis is clear. Autophagy, as part of innate immunity, plays an important role in resistance to viral infection by degrading the virus and promoting the development of innate and adaptive immunity. This study provided evidence that HAdV-B7 infection induced complete autophagic flux, and the pharmacological induction of autophagy decreased HAdV-B7 replication. In this process, the host protein Bcl2-associated athanogene 3 (BAG3) mediated autophagy to inhibit the replication of HAdV-B7 by binding to the PPSY structural domain of viral protein pVI through its WW structural domain. These findings further our understanding of the host immune response during viral infection and will help to develop broad anti-HAdV therapies.

    Reference (39) Relative (20)

    目录

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return