Heat shock protein A1 inhibits the replication of foot-and-mouth disease virus by degrading viral RNA polymerase 3D through chaperone-mediated autophagy. - 2025
Heat shock protein A1 inhibits the replication of foot-and-mouth disease virus by degrading viral RNA polymerase 3D through chaperone-mediated autophagy.
Heat shock protein A1 inhibits the replication of foot-and-mouth disease virus by degrading viral RNA polymerase 3D through chaperone-mediated autophagy.pdf
3D polymerase; HSPA1; RNA dependent RNA polymerase; chaperone mediated autophagy; foot-and-mouth disease virus; heat shock protein
Abstract :
[en] [en] UNLABELLED: Foot-and-mouth disease virus (FMDV), a member of the Picornaviridae family, is a single-stranded, positive-sense RNA virus. Heat shock protein A1 (HSPA1) has been shown to influence the entry, translation, assembly, and release of enterovirus A71 (EV-A71), another Picornaviridae family member. In this study, we demonstrate that HSPA1 plays a different role in the replication of FMDV. By investigating various stages of virus replication, we found that HSPA1 specifically inhibits the RNA replication stage in which HSPA1 inhibits viral RNA replication by degrading the viral RNA-dependent RNA polymerase (RdRp), 3D protein. In the presence of specific inhibitors, we find out that this degradation occurs through the autophagy pathway. Activation and blockage of chaperone-mediated autophagy (CMA) demonstrate that HSPA1 degrades 3D through the CMA pathway. Mutation analysis reveals that 421QEKLI425 is the key motif in 3D responsible for HSPA1-mediated CMA degradation. In summary, this study shows that HSPA1 can degrade the viral 3D protein through the CMA pathway, thereby inhibiting the RNA replication of FMDV and interfering with virus infection. This study, for the first time, demonstrates that HSPA1 employs its chaperone function to mediate the degradation of the FMDV RdRp, revealing the crucial role of HSPA1 in the FMDV infection process and suggesting that HSPA1 could be a potential target for the prevention and treatment of FMDV infection.
IMPORTANCE: Viral RNA replication is the key stage in understanding the pathogenic mechanisms of foot-and-mouth disease virus (FMDV). During this process, the viral non-structural protein 3D serves as an RNA-dependent RNA polymerase (RdRp) to synthesize progeny RNA using the viral genomic RNA as a template. However, the regulatory effect of host cells on FMDV 3D proteins has not yet been studied. In this study, we find that heat shock protein A1 (HSPA1) degrades the viral 3D protein through the chaperone-mediated autophagy (CMA) pathway, thereby inhibiting the RNA replication of FMDV and interfering with virus infection. This study, for the first time, demonstrates that HSPA1 employs its chaperone function to mediate the degradation of the FMDV RdRp.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Ren, Mei ; Université de Liège - ULiège > TERRA Research Centre ; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
Zhou, Haiqian; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
Wu, Jin-En; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
Wang, Jia-Ning; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
Wang, Xuefei; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
Abdullah, Sahibzada Waheed; Livestock and Dairy Development Department Peshawar, Government of Khyber Pakhtunkhwa, Peshawar, Pakistan
Guo, Huichen ; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
Sun, Shiqi ; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
Language :
English
Title :
Heat shock protein A1 inhibits the replication of foot-and-mouth disease virus by degrading viral RNA polymerase 3D through chaperone-mediated autophagy.
Han SC, Guo HC, Sun SQ. 2015. Three-dimensional structure of foot-and-mouth disease virus and its biological functions. Arch Virol 160:1–16. htt ps://doi.org/10.1007/s00705-014-2278-x
World organisation for animal health. Available from: https://www.woah.org/en/home. Accessed March 24, 2025
Brown E, Nelson N, Gubbins S, Colenutt C. 2022. Airborne transmission of foot-and-mouth disease virus: a review of past and present perspectives. Viruses 14:1009. https://doi.org/10.3390/v14051009
Stenfeldt C, Diaz-San Segundo F, de Los Santos T, Rodriguez LL, Arzt J. 2016. The pathogenesis of foot-and-mouth disease in pigs. Front Vet Sci 3:41. https://doi.org/10.3389/fvets.2016.00041
Rodríguez Pulido M, Sáiz M. 2017. Molecular mechanisms of foot-and-mouth disease virus targeting the host antiviral response. Front Cell Infect Microbiol 7:252. https://doi.org/10.3389/fcimb.2017.00252
Logan G, Newman J, Wright CF, Lasecka-Dykes L, Haydon DT, Cottam EM, Tuthill TJ. 2018. Deep sequencing of foot-and-mouth disease virus reveals RNA sequences involved in genome packaging. J Virol 92:e01159-17. https://doi.org/10.1128/JVI.01159-17
Gao Y, Sun SQ, Guo HC. 2016. Biological function of Foot-and-mouth disease virus non-structural proteins and non-coding elements. Virol J 13:107. https://doi.org/10.1186/s12985-016-0561-z
Kampinga HH, Hageman J, Vos MJ, Kubota H, Tanguay RM, Bruford EA, Cheetham ME, Chen B, Hightower LE. 2009. Guidelines for the nomenclature of the human heat shock proteins. Cell Stress Chaperones 14:105–111. https://doi.org/10.1007/s12192-008-0068-7
Geller R, Pechmann S, Acevedo A, Andino R, Frydman J. 2018. Hsp90 shapes protein and RNA evolution to balance trade-offs between protein stability and aggregation. Nat Commun 9:1781. https://doi.org/10.1038/s41467-018-04203-x
Sarnow P. 1989. Translation of glucose-regulated protein 78/immunoglobulin heavy-chain binding protein mRNA is increased in poliovirus-infected cells at a time when cap-dependent translation of cellular mRNAs is inhibited. Proc Natl Acad Sci U S A 86:5795–5799. https://doi.org/10.1073/pnas.86.15.5795
Xu T, Lin Z, Wang C, Li Y, Xia Y, Zhao M, Hua L, Chen Y, Guo M, Zhu B. 2019. Heat shock protein 70 as a supplementary receptor facilitates enterovirus 71 infections in vitro. Microb Pathog 128:106–111. https://doi.org/10.1016/j.micpath.2018.12.032
Wang RYL, Kuo R-L, Ma W-C, Huang H-I, Yu J-S, Yen S-M, Huang C-R, Shih S-R. 2013. Heat shock protein-90-beta facilitates enterovirus 71 viral particles assembly. Virology (Auckl) 443:236–247. https://doi.org/10.1016/j.virol.2013.05.001
Tsou YL, Lin YW, Chang HW, Lin HY, Shao HY, Yu SL, Liu CC, Chitra E, Sia C, Chow YH. 2013. Heat shock protein 90: role in enterovirus 71 entry and assembly and potential target for therapy. PLoS One 8:e77133. https://doi.org/10.1371/journal.pone.0077133
Su YS, Hwang LH, Chen CJ. 2021. Heat shock protein A6, a novel HSP70, is induced during enterovirus A71 infection to facilitate internal ribosomal entry site-mediated translation. Front Microbiol 12:664955. ht tps://doi.org/10.3389/fmicb.2021.664955
Su YS, Hsieh PY, Li JS, Pao YH, Chen CJ, Hwang LH. 2020. The heat shock protein 70 family of chaperones regulates all phases of the enterovirus A71 life cycle. Front Microbiol 11:1656. https://doi.org/10.3389/fmicb.2020.01656
Tang J, Abdullah SW, Li P, Wu J, Pei C, Mu S, Wang Y, Sun S, Guo H. 2022. Heat shock protein 60 is involved in viral replication complex formation and facilitates foot and mouth virus replication by stabilizing viral nonstructural proteins 3A and 2C. MBio 13:e0143422. https://doi.org/10.1128/mbio.01434-22
Tian G, Hu C, Yun Y, Yang W, Dubiel W, Cheng Y, Wolf DA. 2021. Dual roles of HSP70 chaperone HSPA1 in quality control of nascent and newly synthesized proteins. EMBO J 40:e106183. https://doi.org/10.15252/embj.2020106183
Zhi X, Zhang Y, Sun S, Zhang Z, Dong H, Luo X, Wei Y, Lu Z, Dou Y, Wu R, Jiang Z, Weng C, Seong Seo H, Guo H. 2020. NLRP3 inflammasome activation by Foot-and-mouth disease virus infection mainly induced by viral RNA and non-structural protein 2B. RNA Biol 17:335–349. https://doi.org/10.1080/15476286.2019.1700058
Han S, Sun S, Li P, Liu Q, Zhang Z, Dong H, Sun M, Wu W, Wang X, Guo H. 2020. Ribosomal protein L13 promotes IRES-driven translation of foot- and-mouth disease virus in a helicase DDX3-dependent manner. J Virol 94:e01679-19. https://doi.org/10.1128/JVI.01679-19
Wang X, Abdullah SW, Wu J, Tang J, Zhang Y, Dong H, Bai M, Wei S, Sun S, Guo H. 2023. Foot-and-mouth disease virus downregulates vacuolar protein sorting 28 to promote viral replication. J Virol 97:e0018123. https://doi.org/10.1128/jvi.00181-23
Wu J, Sun C, Guan J, Abdullah SW, Wang X, Ren M, Qiao L, Sun S, Guo H. 2024. Nuclear ribonucleoprotein RALY downregulates foot-and-mouth disease virus replication but antagonized by viral 3C protease. Microbiol Spectr 12:e0365823. https://doi.org/10.1128/spectrum.03658-23
Abdullah SW, Han S, Wu J, Zhang Y, Bai M, Jin Y, Zhi X, Guan J, Sun S, Guo H. 2020. The DDX23 negatively regulates translation and replication of foot-and-mouth disease virus and is degraded by 3C proteinase. Viruses 12:1348. https://doi.org/10.3390/v12121348
Abdullah SW, Wu J, Zhang Y, Bai M, Guan J, Liu X, Sun S, Guo H. 2021. DDX21, a host restriction factor of FMDV IRES-dependent translation and replication. Viruses 13:1765. https://doi.org/10.3390/v13091765
Wang Y, Mao Q, Chang H, Wu Y, Pan S, Li Y, Zhang Y. 2016. Inability of FMDV replication in equine kidney epithelial cells is independent of integrin αvβ3 and αvβ6. Virology (Auckl) 492:251–258. https://doi.org/10.1016/j.virol.2016.01.025
Neff S, Sá-Carvalho D, Rieder E, Mason PW, Blystone SD, Brown EJ, Baxt B. 1998. Foot-and-mouth disease virus virulent for cattle utilizes the integrin alpha(v)beta3 as its receptor. J Virol 72:3587–3594. https://doi.org/10.1128/JVI.72.5.3587-3594.1998
Jackson T, Ellard FM, Ghazaleh RA, Brookes SM, Blakemore WE, Corteyn AH, Stuart DI, Newman JW, King AM. 1996. Efficient infection of cells in culture by type O foot-and-mouth disease virus requires binding to cell surface heparan sulfate. J Virol 70:5282–5287. https://doi.org/10.1128/JVI.70.8.5282-5287.1996
Bilog AD, Smulders L, Oliverio R, Labanieh C, Zapanta J, Stahelin RV, Nikolaidis N. 2019. Membrane localization of HspA1A, a stress inducible 70-kda heat-shock protein, depends on its interaction with intracellular phosphatidylserine. Biomolecules 9:152. https://doi.org/10.3390/biom9 040152
Horsington J, Zhang Z. 2007. Analysis of foot-and-mouth disease virus replication using strand-specific quantitative RT-PCR. J Virol Methods 144:149–155. https://doi.org/10.1016/j.jviromet.2007.05.002
Monaghan P, Cook H, Jackson T, Ryan M, Wileman T. 2004. The ultrastructure of the developing replication site in foot-and-mouth disease virus-infected BHK-38 cells. J Gen Virol 85:933–946. https://doi.org/10.1099/vir.0.19408-0
Tao YJ, Ye Q. 2010. RNA virus replication complexes. PLoS Pathog 6:e1000943. https://doi.org/10.1371/journal.ppat.1000943
Lasecka-Dykes L, Tulloch F, Simmonds P, Luke GA, Ribeca P, Gold S, Knowles NJ, Wright CF, Wadsworth J, Azhar M, King DP, Tuthill TJ, Jackson T, Ryan MD. 2021. Mutagenesis mapping of RNA structures within the foot-and-mouth disease virus genome reveals functional elements localized in the polymerase (3Dpol)-encoding region. mSphere 6:e0001521. https://doi.org/10.1128/mSphere.00015-21
Gladue DP, O’Donnell V, Baker-Bransetter R, Pacheco JM, Holinka LG, Arzt J, Pauszek S, Fernandez-Sainz I, Fletcher P, Brocchi E, Lu Z, Rodriguez LL, Borca MV. 2014. Interaction of foot-and-mouth disease virus nonstructural protein 3A with host protein DCTN3 is important for viral virulence in cattle. J Virol 88:2737–2747. https://doi.org/10.1128/JVI.030 59-13
Gladue DP, O’Donnell V, Baker-Branstetter R, Holinka LG, Pacheco JM, Fernandez-Sainz I, Lu Z, Brocchi E, Baxt B, Piccone ME, Rodriguez L, Borca MV. 2012. Foot-and-mouth disease virus nonstructural protein 2C interacts with Beclin1, modulating virus replication. J Virol 86:12080–12090. https://doi.org/10.1128/JVI.01610-12
Medina GN, Knudsen GM, Greninger AL, Kloc A, Díaz-San Segundo F, Rieder E, Grubman MJ, DeRisi JL, de Los Santos T. 2017. Interaction between FMDV Lpro and transcription factor ADNP is required for optimal viral replication. Virology (Auckl) 505:12–22. https://doi.org/10.1016/j.virol.2017.02.010
Mayer MP, Bukau B. 2005. Hsp70 chaperones: cellular functions and molecular mechanism. Cell Mol Life Sci 62:670–684. https://doi.org/10.1007/s00018-004-4464-6
Aoki H, Kondo Y, Aldape K, Yamamoto A, Iwado E, Yokoyama T, Hollingsworth EF, Kobayashi R, Hess K, Shinojima N, Shingu T, Tamada Y, Zhang L, Conrad C, Bogler O, Mills G, Sawaya R, Kondo S. 2008. Monitoring autophagy in glioblastoma with antibody against isoform B of human microtubule-associated protein 1 light chain 3. Autophagy 4:467–475. https://doi.org/10.4161/auto.5668
Huang Y, Feng Y, Cui L, Yang L, Zhang Q, Zhang J, Jiang X, Zhang X, Lv Y, Jia JZ, Zhang DX, Huang YS. 2021. Autophagy-related LC3 accumulation interacted directly with LIR containing RIPK1 and RIPK3, stimulating necroptosis in hypoxic cardiomyocytes. Front Cell Dev Biol 9:679637. htt ps://doi.org/10.3389/fcell.2021.679637
Wang T, Zhang L, Liang W, Liu S, Deng W, Liu Y, Liu Y, Song M, Guo K, Zhang Y. 2022. Extracellular vesicles originating from autophagy mediate an antibody-resistant spread of classical swine fever virus in cell culture. Autophagy 18:1433–1449. https://doi.org/10.1080/15548627.2021.1987673
Kaushik S, Cuervo AM. 2018. The coming of age of chaperone-mediated autophagy. Nat Rev Mol Cell Biol 19:365–381. https://doi.org/10.1038/s4 1580-018-0001-6
Kirchner P, Bourdenx M, Madrigal-Matute J, Tiano S, Diaz A, Bartholdy BA, Will B, Cuervo AM. 2019. Proteome-wide analysis of chaperone-mediated autophagy targeting motifs. PLoS Biol 17:e3000301. https://doi.org/10.1371/journal.pbio.3000301
Qiao L, Hu J, Qiu X, Wang C, Peng J, Zhang C, Zhang M, Lu H, Chen W. 2023. LAMP2A, LAMP2B and LAMP2C: similar structures, divergent roles. Autophagy 19:2837–2852. https://doi.org/10.1080/15548627.2023.2235 196
Zhang J, Huang J, Gu Y, Xue M, Qian F, Wang B, Yang W, Yu H, Wang Q, Guo X, Ding X, Wang J, Jin M, Zhang Y. 2021. Inflammation-induced inhibition of chaperone-mediated autophagy maintains the immunosuppressive function of murine mesenchymal stromal cells. Cell Mol Immunol 18:1476–1488. https://doi.org/10.1038/s41423-019-0345-7
Kim HJ, Koh HC. 2021. Chaperon-mediated autophagy can regulate diquat-induced apoptosis by inhibiting α-synuclein accumulation cooperatively with macroautophagy. Food Chem Toxicol 158:112706. htt ps://doi.org/10.1016/j.fct.2021.112706
Zhao X, Di Q, Yu J, Quan J, Xiao Y, Zhu H, Li H, Ling J, Chen W. 2022. USP19 (ubiquitin specific peptidase 19) promotes TBK1 (TANK-binding kinase 1) degradation via chaperone-mediated autophagy. Autophagy 18:891–908. https://doi.org/10.1080/15548627.2021.1963155
Kempf BJ, Barton DJ. 2015. Picornavirus RNA polyadenylation by 3D(pol), the viral RNA-dependent RNA polymerase. Virus Res 206:3–11. https://doi.org/10.1016/j.virusres.2014.12.030
Kempf BJ, Kelly MM, Springer CL, Peersen OB, Barton DJ. 2013. Structural features of a picornavirus polymerase involved in the polyadenylation of viral RNA. J Virol 87:5629–5644. https://doi.org/10.1128/JVI.02590-12
Ferrer-Orta C, Arias A, Perez-Luque R, Escarmís C, Domingo E, Verdaguer N. 2004. Structure of foot-and-mouth disease virus RNA-dependent RNA polymerase and its complex with a template-primer RNA. J Biol Chem 279:47212–47221. https://doi.org/10.1074/jbc.M405465200
Gruez A, Selisko B, Roberts M, Bricogne G, Bussetta C, Jabafi I, Coutard B, De Palma AM, Neyts J, Canard B. 2008. The crystal structure of coxsackievirus B3 RNA-dependent RNA polymerase in complex with its protein primer VPg confirms the existence of a second VPg binding site on Picornaviridae polymerases. J Virol 82:9577–9590. https://doi.org/10.1128/JVI.00631-08
Chen C, Wang Y, Shan C, Sun Y, Xu P, Zhou H, Yang C, Shi PY, Rao Z, Zhang B, Lou Z. 2013. Crystal structure of enterovirus 71 RNA-dependent RNA polymerase complexed with its protein primer VPg: implication for a trans mechanism of VPg uridylylation. J Virol 87:5755–5768. https://doi.org/10.1128/JVI.02733-12
Iyer K, Chand K, Mitra A, Trivedi J, Mitra D. 2021. Diversity in heat shock protein families: functional implications in virus infection with a comprehensive insight of their role in the HIV-1 life cycle. Cell Stress Chaperones 26:743–768. https://doi.org/10.1007/s12192-021-01223-3
Kotler JLM, Street TO. 2023. Mechanisms of protein quality control in the endoplasmic reticulum by a coordinated Hsp40-Hsp70-Hsp90 system. Annu Rev Biophys 52:509–524. https://doi.org/10.1146/annurev-biophys -111622-091309
Singh MK, Shin Y, Ju S, Han S, Choe W, Yoon KS, Kim SS, Kang I. 2024. Heat shock response and heat shock proteins: current understanding and future opportunities in human diseases. IJMS 25:4209. https://doi.org/10.3390/ijms25084209
Zhou C, Liu Y, Wei Q, Chen Y, Yang S, Cheng A, Zhang G. 2023. HSPA5 promotes attachment and internalization of porcine epidemic diarrhea virus through interaction with the spike protein and the endo-/ lysosomal pathway. J Virol 97:e0054923. https://doi.org/10.1128/jvi.0054 9-23
Taguwa S, Maringer K, Li X, Bernal-Rubio D, Rauch JN, Gestwicki JE, Andino R, Fernandez-Sesma A, Frydman J. 2015. Defining Hsp70 subnetworks in dengue virus replication reveals key vulnerability in flavivirus infection. Cell 163:1108–1123. https://doi.org/10.1016/j.cell.2015.10.046
Chen N, Liu Y, Bai T, Chen J, Zhao Z, Li J, Shao B, Zhang Z, Zhou Y, Wang X, Zhu Z. 2022. Quercetin inhibits Hsp70 blocking of bovine viral diarrhea virus infection and replication in the early stage of virus infection. Viruses 14:2365. https://doi.org/10.3390/v14112365
Pujhari S, Brustolin M, Macias VM, Nissly RH, Nomura M, Kuchipudi SV, Rasgon JL. 2019. Heat shock protein 70 (Hsp70) mediates Zika virus entry, replication, and egress from host cells. Emerg Microbes Infect 8:8–16. https://doi.org/10.1080/22221751.2018.1557988
Oh W, Song J. 2006. Hsp70 functions as a negative regulator of West Nile virus capsid protein through direct interaction. Biochem Biophys Res Commun 347:994–1000. https://doi.org/10.1016/j.bbrc.2006.06.190
Li G, Zhang J, Tong X, Liu W, Ye X. 2011. Heat shock protein 70 inhibits the activity of Influenza A virus ribonucleoprotein and blocks the replication of virus in vitro and in vivo. PLoS One 6:e16546. https://doi.org/10.1371/journal.pone.0016546
Wang G, Wang Y, Shang Y, Zhang Z, Liu X. 2015. How foot-and-mouth disease virus receptor mediates foot-and-mouth disease virus infection. Virol J 12:9. https://doi.org/10.1186/s12985-015-0246-z
Kobayashi K, Koike S. 2020. Cellular receptors for enterovirus A71. J Biomed Sci 27:23. https://doi.org/10.1186/s12929-020-0615-9
Rossmann MG, He Y, Kuhn RJ. 2002. Picornavirus-receptor interactions. Trends Microbiol 10:324–331. https://doi.org/10.1016/s0966-842x(02)02 383-1
Fry EE, Lea SM, Jackson T, Newman JW, Ellard FM, Blakemore WE, Abu-Ghazaleh R, Samuel A, King AM, Stuart DI. 1999. The structure and function of a foot-and-mouth disease virus-oligosaccharide receptor complex. EMBO J 18:543–554. https://doi.org/10.1093/emboj/18.3.543
Ruiz-Sáenz J, Goez Y, Tabares W, López-Herrera A. 2009. Cellular receptors for foot and mouth disease virus. Intervirology 52:201–212. htt ps://doi.org/10.1159/000226121
Jiang P, Liu Y, Ma HC, Paul AV, Wimmer E. 2014. Picornavirus morphogenesis. Microbiol Mol Biol Rev 78:418–437. https://doi.org/10.1128/MMBR.00012-14
Belsham GJ. 2005. Translation and replication of FMDV RNA. Curr Top Microbiol Immunol 288:43–70. https://doi.org/10.1007/3-540-27109-0_3
Novak JE, Kirkegaard K. 1991. Improved method for detecting poliovirus negative strands used to demonstrate specificity of positive-strand encapsidation and the ratio of positive to negative strands in infected cells. J Virol 65:3384–3387. https://doi.org/10.1128/JVI.65.6.3384-3387.1 991
Wu J, Zhang Z, Teng Z, Abdullah SW, Sun S, Guo H. 2021. Sec62 regulates endoplasmic reticulum stress and autophagy balance to affect foot-and-mouth disease virus replication. Front Cell Infect Microbiol 11:707107. ht tps://doi.org/10.3389/fcimb.2021.707107
Liu H, Xue Q, Yang F, Cao W, Liu P, Liu X, Zhu Z, Zheng H. 2024. Foot-and-mouth disease virus VP1 degrades YTHDF2 through autophagy to regulate IRF3 activity for viral replication. Autophagy 20:1597–1615. http s://doi.org/10.1080/15548627.2024.2330105
Zhang H, Wang X, Qu M, Li Z, Yin X, Tang L, Liu X, Sun Y. 2023. Foot-and-mouth disease virus structural protein VP3 interacts with HDAC8 and promotes its autophagic degradation to facilitate viral replication. Autophagy 19:2869–2883. https://doi.org/10.1080/15548627.2023.2233 847
O’Donnell V, Pacheco JM, LaRocco M, Burrage T, Jackson W, Rodriguez LL, Borca MV, Baxt B. 2011. Foot-and-mouth disease virus utilizes an autophagic pathway during viral replication. Virology (Auckl) 410:142–150. https://doi.org/10.1016/j.virol.2010.10.042
Tasnin MN, Takahashi Y, Takuma T, Ushimaru T. 2025. ESCRT mediates micronucleophagy and macronucleophagy in yeast. Biochem Biophys Res Commun 742:151102. https://doi.org/10.1016/j.bbrc.2024.151102
Qiu Y, Ye X, Hanson PJ, Zhang HM, Zong J, Cho B, Yang D. 2016. Hsp70-1: upregulation via selective phosphorylation of heat shock factor 1 during coxsackieviral infection and promotion of viral replication via the AU-rich element. Cell Mol Life Sci 73:1067–1084. https://doi.org/10.1007/s00 018-015-2036-6
Wang F, Qiu Y, Zhang HM, Hanson P, Ye X, Zhao G, Xie R, Tong L, Yang D. 2017. Heat shock protein 70 promotes coxsackievirus B3 translation initiation and elongation via Akt-mTORC1 pathway depending on activation of p70S6K and Cdc2. Cell Microbiol 19:e12725. https://doi.org/10.1111/cmi.12725
