Citation: Lin Jiang, Xinhong Tian, Keran Ma, Wentao Qiao, Juan Tan. RNF152 regulates prototype foamy virus replication by targeting Gag polyubiquitination and VLPs production .VIROLOGICA SINICA, 2026, 41(5) : 1078-1090.  http://dx.doi.org/10.1016/j.virs.2026.08.016

RNF152 regulates prototype foamy virus replication by targeting Gag polyubiquitination and VLPs production

  • Prototype foamy viruses (PFVs) are complex retroviruses that establish long-term latent infections in hosts without causing disease, positioning them as potential safe gene transfer vectors. Understanding the host proteins involved in PFV replication and their interaction mechanisms may enhance gene transfer efficiency. However, only a few cellular proteins are known to influence PFV replication. Based on the transcriptomic analysis of PFV-infected HT1080 cells, we observed a potential significance of RING finger protein 152 (RNF152) in modulating PFV replication. Overexpression of RNF152 significantly inhibits PFV replication, whereas RNF152 knockdown enhances viral replication. Mechanistically, RNF152 interacts with the Gag protein to promote its polyubiquitination at lysine 396 (K396), thereby facilitating its degradation via the ubiquitin-proteasome system. Furthermore, RNF152 reduces the size and number of PFV virus-like particles (VLPs) by inhibiting the multimerization of Gag. Collectively, our findings reveal a previously unrecognized mechanism that influences PFV infection. Additionally, we elucidate the role of RNF152 in affecting virus replication for the first time, providing valuable insights into the mechanisms of virus replication and demonstrating the importance of ubiquitination modification in affecting viral replication.

  • 加载中
  • 10.1016j.virs.2026.08.016-ESM.docx
    1. Achong, B.G., Mansell, P.W., Epstein, M.A.,Clifford, P., 1971. An unusual virus in cultures from a human nasopharyngeal carcinoma. J Natl Cancer Inst, 46, 299-307.

    2. Boutin, J.A., 1997. Myristoylation. Cell Signal, 9, 15-35.

    3. Braun, E., Hotter, D., Koepke, L., Zech, F., Gross, R., Sparrer, K.M.J., Muller, J.A., Pfaller, C.K., Heusinger, E., Wombacher, R., et al., 2019. Guanylate-Binding Proteins 2 and 5 Exert Broad Antiviral Activity by Inhibiting Furin-Mediated Processing of Viral Envelope Proteins. Cell Rep, 27, 2092-2104.e2010.

    4. Broussard, S.R., Comuzzie, A.G., Leighton, K.L., Leland, M.M., Whitehead, E.M.,Allan, J.S., 1997. Characterization of new simian foamy viruses from African nonhuman primates. Virology, 237, 349-359.

    5. Charoenthongtrakul, S., Gao, L., Parvatiyar, K., Lee, D.,Harhaj, E.W., 2013. RING finger protein 11 targets TBK1/IKKi kinases to inhibit antiviral signaling. PLoS One, 8, e53717.

    6. Chougui, G., Munir-Matloob, S., Matkovic, R., Martin, M.M., Morel, M., Lahouassa, H., Leduc, M., Ramirez, B.C., Etienne, L.,Margottin-Goguet, F., 2018. HIV-2/SIV viral protein X counteracts HUSH repressor complex. Nat Microbiol, 3, 891-897.

    7. Compton, A.A., Bruel, T., Porrot, F., Mallet, A., Sachse, M., Euvrard, M., Liang, C., Casartelli, N.,Schwartz, O., 2014. IFITM proteins incorporated into HIV-1 virions impair viral fusion and spread. Cell Host Microbe, 16, 736-747.

    8. Demirov, D.G.,Freed, E.O., 2004. Retrovirus budding. Virus Res, 106, 87-102.

    9. Deng, L., Chen, L., Zhao, L., Xu, Y., Peng, X., Wang, X., Ding, L., Jin, J., Teng, H., Wang, Y., Pan, W., Yu, F., Liao, L., Li, L., Ge, X.,Wang, P., 2019. Ubiquitination of Rheb governs growth factor-induced mTORC1 activation. Cell Res, 29, 136-150.

    10. Deng, L., Jiang, C., Chen, L., Jin, J., Wei, J., Zhao, L., Chen, M., Pan, W., Xu, Y., Chu, H., Wang, X., Ge, X., Li, D., Liao, L., Liu, M., Li, L.,Wang, P., 2015. The ubiquitination of rag A GTPase by RNF152 negatively regulates mTORC1 activation. Mol Cell, 58, 804-818.

    11. Dong, L., Cheng, Q., Wang, Z., Yuan, P., Li, Z., Sun, Y., Han, S., Yin, J., Peng, B., He, X.,Liu, W., 2015. Human Pirh2 is a novel inhibitor of prototype foamy virus replication. Viruses, 7, 1668-1684.

    12. Eastman, S.W.,Linial, M.L., 2001. Identification of a conserved residue of foamy virus Gag required for intracellular capsid assembly. J Virol, 75, 6857-6864.

    13. Enders, J.F.,Peebles, T.C., 1954. Propagation in tissue cultures of cytopathogenic agents from patients with measles. Proc Soc Exp Biol Med, 86, 277-286.

    14. Ficarelli, M., Wilson, H., Pedro Galao, R., Mazzon, M., Antzin-Anduetza, I., Marsh, M., Neil, S.J.,Swanson, C.M., 2019. KHNYN is essential for the zinc finger antiviral protein (ZAP) to restrict HIV-1 containing clustered CpG dinucleotides. Elife, 9, e46767.

    15. Goldstone, D.C., Flower, T.G., Ball, N.J., Sanz-Ramos, M., Yap, M.W., Ogrodowicz, R.W., Stanke, N., Reh, J., Lindemann, D., Stoye, J.P.,Taylor, I.A., 2013. A unique spumavirus Gag N-terminal domain with functional properties of orthoretroviral matrix and capsid. PLoS Pathog, 9, e1003376.

    16. Guo, G., Wang, Y., Hu, X.M., Li, Z.R., Tan, J.,Qiao, W.T., 2021. Human Schlafen 11 exploits codon preference discrimination to attenuate viral protein synthesis of prototype foamy virus (PFV). Virology, 555, 78-88.

    17. Hu, X., Yang, W., Liu, R., Geng, Y., Qiao, W.,Tan, J., 2014. N-Myc interactor inhibits prototype foamy virus by sequestering viral Tas protein in the cytoplasm. J Virol, 88, 7036-7044.

    18. Jiang, L., Han, C., Zhang, J., Li, G., Qiao, W.,Tan, J., 2025. VCY mediates inhibition of PFV replication via interaction with the transcription activator Tas. J Virol, 99, e0016625.

    19. Johnson, R.H., Oginnusi, A.A.,Ladds, P.W., 1983. Isolations and serology of bovine spumavirus. Australian Veterinary Journal, 60, 147-147.

    20. Kane, M., Mele, V., Liberatore, R.A.,Bieniasz, P.D., 2020. Inhibition of spumavirus gene expression by PHF11. PLoS pathogens, 16, e1008644.

    21. Kim, Y.J., Lee, Y., Shin, H., Hwang, S., Park, J.,Song, E.J., 2023. Ubiquitin-proteasome system as a target for anticancer treatment-an update. Arch Pharm Res, 46, 573-597.

    22. Lahouassa, H., Daddacha, W., Hofmann, H., Ayinde, D., Logue, E.C., Dragin, L., Bloch, N., Maudet, C., Bertrand, M., Gramberg, T., Pancino, G., Priet, S., Canard, B., Laguette, N., Benkirane, M., Transy, C., Landau, N.R., Kim, B.,Margottin-Goguet, F., 2012. SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates. Nat Immunol, 13, 223-228.

    23. Li, W., Ma, Y., He, L., Li, H., Chu, Y., Jiang, Z., Zhao, X., Nie, Y., Wang, X.,Wang, H., 2021. Protease-activated receptor 2 stabilizes Bcl-xL and regulates EGFR-targeted therapy response in colorectal cancer. Cancer Lett, 517, 14-23.

    24. Li, Y., Ozaki, T., Kikuchi, H., Yamamoto, H., Ohira, M.,Nakagawara, A., 2008. A novel HECT-type E3 ubiquitin protein ligase NEDL1 enhances the p53-mediated apoptotic cell death in its catalytic activity-independent manner. Oncogene, 27, 3700-3709.

    25. Li, Z., Hao, P., Zhao, Z., Gao, W., Huan, C., Li, L., Chen, X., Wang, H., Jin, N., Luo, Z.Q., Li, C.,Zhang, W., 2023. The E3 ligase RNF5 restricts SARS-CoV-2 replication by targeting its envelope protein for degradation. Signal Transduct Target Ther, 8, 53.

    26. Life, R.B., Lee, E.G., Eastman, S.W.,Linial, M.L., 2008. Mutations in the amino terminus of foamy virus Gag disrupt morphology and infectivity but do not target assembly. J Virol, 82, 6109-6119.

    27. Lin, L., Wang, X., Chen, Z., Deng, T., Yan, Y., Dong, W., Huang, Y.,Zhou, J., 2023. TRIM21 restricts influenza A virus replication by ubiquitination-dependent degradation of M1. PLoS Pathog, 19, e1011472.

    28. Lindemann, D.,Rethwilm, A., 2011. Foamy virus biology and its application for vector development. Viruses, 3, 561-585.

    29. Liu, R., Lin, Y., Jia, R., Geng, Y., Liang, C., Tan, J.,Qiao, W., 2014. HIV-1 Vpr stimulates NF-κB and AP-1 signaling by activating TAK1. Retrovirology, 11, 45.

    30. Liu, Y., Betts, M.J., Lei, J., Wei, G., Bao, Q., Kehl, T., Russell, R.B.,Lochelt, M., 2016. Mutagenesis of N-terminal residues of feline foamy virus Gag reveals entirely distinct functions during capsid formation, particle assembly, Gag processing and budding. Retrovirology, 13, 57.

    31. Lochelt, M., Romen, F., Bastone, P., Muckenfuss, H., Kirchner, N., Kim, Y.B., Truyen, U., Rosler, U., Battenberg, M., Saib, A., Flory, E., Cichutek, K.,Munk, C., 2005. The antiretroviral activity of APOBEC3 is inhibited by the foamy virus accessory Bet protein. Proc Natl Acad Sci U S A, 102, 7982-7987.

    32. Luo, Q., Liu, Q., Cheng, H., Wang, J., Zhao, T., Zhang, J., Mu, C., Meng, Y., Chen, L., Zhou, C., Lei, H., Yang, J., Chen, G., Li, Y., Pan, L., Chen, Q.,Zhu, Y., 2022. Nondegradable ubiquitinated ATG9A organizes Golgi integrity and dynamics upon stresses. Cell Rep, 40, 111195.

    33. Martin, D.D., Beauchamp, E.,Berthiaume, L.G., 2011. Post-translational myristoylation: Fat matters in cellular life and death. Biochimie, 93, 18-31.

    34. Mello-Vieira, J., Bopp, T.,Dikic, I., 2023. Ubiquitination and cell-autonomous immunity. Curr Opin Immunol, 84, 102368.

    35. Metzner, F.J., Wenzl, S.J., Kugler, M., Krebs, S., Hopfner, K.P.,Lammens, K., 2022. Mechanistic understanding of human SLFN11. Nat Commun, 13, 5464.

    36. Miyakawa, K., Ryo, A., Murakami, T., Ohba, K., Yamaoka, S., Fukuda, M., Guatelli, J.,Yamamoto, N., 2009. BCA2/Rabring7 promotes tetherin-dependent HIV-1 restriction. PLoS Pathog, 5, e1000700.

    37. Mochizuki, M., Akuzawa, M.,Nagatomo, H., 1990. Serological survey of the Iriomote cat (Felis iriomotensis) in Japan. J Wildl Dis, 26, 236-245.

    38. Murray, S.M.,Linial, M.L., 2019. Simian Foamy Virus Co-Infections. Viruses, 11, 902.

    39. Neil, S.J., Zang, T.,Bieniasz, P.D., 2008. Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature, 451, 425-430.

    40. Netzer, K.O., Rethwilm, A., Maurer, B.,Ter Meulen, V., 1990. Identification of the major immunogenic structural proteins of human foamy virus. J Gen Virol, 71 ( Pt 5), 1237-1241.

    41. Park, I.W., Han, C., Song, X., Green, L.A., Wang, T., Liu, Y., Cen, C., Song, X., Yang, B., Chen, G.,He, J.J., 2009. Inhibition of HIV-1 entry by extracts derived from traditional Chinese medicinal herbal plants. BMC Complement Altern Med, 9, 29.

    42. Pyeon, D., Timani, K.A., Gulraiz, F., He, J.J.,Park, I.W., 2016. Function of ubiquitin (Ub) specific protease 15 (USP15) in HIV-1 replication and viral protein degradation. Virus Res, 223, 161-169.

    43. Reh, J., Stange, A., Gotz, A., Ronitz, M., Grosse, A.,Lindemann, D., 2013. An N-terminal domain helical motif of Prototype Foamy Virus Gag with dual functions essential for particle egress and viral infectivity. Retrovirology, 10, 45.

    44. Saulle, I., Ibba, S.V., Vittori, C., Fenizia, C., Mercurio, V., Vichi, F., Caputo, S.L., Trabattoni, D., Clerici, M.,Biasin, M., 2020. Sterol metabolism modulates susceptibility to HIV-1 Infection. Aids, 34, 1593-1602.

    45. Scott, T.M., Arnold, L.M., Powers, J.A., Mccann, D.A., Rowe, A.B., Christensen, D.E., Pereira, M.J., Zhou, W., Torrez, R.M., Iwasa, J.H., Kranzusch, P.J., Sundquist, W.I.,Johnson, J.S., 2025. Cell-free assays reveal that the HIV-1 capsid protects reverse transcripts from cGAS immune sensing. PLoS Pathog, 21, e1012206.

    46. Senft, D., Qi, J.,Ronai, Z.A., 2018. Ubiquitin ligases in oncogenic transformation and cancer therapy. Nat Rev Cancer, 18, 69-88.

    47. Shi, H., Quan, P., Tang, C., Hou, Y., Wang, H., Wang, Y., Wang, H.,Zhang, W., 2026. ZNF598 enhances FAT10-mediated non-covalent stabilization of Tat to promote HIV-1 transcription and replication. Virol Sin, 10.1016/j.virs.2026.07.007.

    48. Smaga, S.S., Xu, C., Summers, B.J., Digianantonio, K.M., Perilla, J.R.,Xiong, Y., 2019. MxB Restricts HIV-1 by Targeting the Tri-hexamer Interface of the Viral Capsid. Structure, 27, 1234-1245.

    49. Song, Y.H., Kim, H., Baur, A.S.,Lee, J.H., 2025. Uncovering the evolving arms race between host immunity and HIV-1. Trends Immunol, 46, 728-740.

    50. Stange, A., Luftenegger, D., Reh, J., Weissenhorn, W.,Lindemann, D., 2008. Subviral particle release determinants of prototype foamy virus. J Virol, 82, 9858-9869.

    51. Stanke, N., Stange, A., Luftenegger, D., Zentgraf, H.,Lindemann, D., 2005. Ubiquitination of the prototype foamy virus envelope glycoprotein leader peptide regulates subviral particle release. J Virol, 79, 15074-15083.

    52. Swiersy, A., Wiek, C., Zentgraf, H.,Lindemann, D., 2013. Characterization and manipulation of foamy virus membrane interactions. Cell Microbiol, 15, 227-236.

    53. Tai, H.Y., Sun, K.H., Kung, S.H.,Liu, W.T., 2001. A quantitative assay for measuring human foamy virus using an established indicator cell line. J Virol Methods, 94, 155-162.

    54. Takeshita, F., Ishii, K.J., Kobiyama, K., Kojima, Y., Coban, C., Sasaki, S., Ishii, N., Klinman, D.M., Okuda, K., Akira, S.,Suzuki, K., 2005. TRAF4 acts as a silencer in TLR-mediated signaling through the association with TRAF6 and TRIF. Eur J Immunol, 35, 2477-2485.

    55. Tao, Y., Gong, Z., Shen, S., Ding, Y., Zan, R., Zheng, B., Sun, W., Ma, C., Shu, M., Lu, X., Liu, H., Ni, X., Liu, H.,Suo, T., 2024. Fasting-induced RNF152 resensitizes gallbladder cancer cells to gemcitabine by inhibiting mTORC1-mediated glycolysis. iScience, 27, 109659.

    56. Tobaly-Tapiero, J., Bittoun, P., Neves, M., Guillemin, M.C., Lecellier, C.H., Puvion-Dutilleul, F., Gicquel, B., Zientara, S., Giron, M.L., De The, H.,Saib, A., 2000. Isolation and characterization of an equine foamy virus. J Virol, 74, 4064-4073.

    57. Umthong, S., Timilsina, U., D'angelo, M.R., Salka, K.,Stavrou, S., 2024. MARCH2, a T cell specific factor that restricts HIV-1 infection. PLoS Pathog, 20, e1012330.

    58. Wan, J., Liu, S., Sun, W., Yu, H., Tang, W., Liu, W., Ji, J.,Liu, B., 2021. Ring finger protein 152-dependent degradation of TSPAN12 suppresses hepatocellular carcinoma progression. Cancer Cell Int, 21, 122.

    59. Wang, F., Hao, P., Pu, Y., He, X., He, Q., Cui, H.,Jiang, S., 2025. KDM1A-driven RNF81 downregulation promotes gastric cancer progression via KLF4 destabilization. Oncogene, 44, 3864-3878.

    60. Wang, S., Yang, Y.K., Chen, T., Zhang, H., Yang, W.W., Song, S.S., Zhai, Z.H.,Chen, D.Y., 2016. RNF123 has an E3 ligase-independent function in RIG-I-like receptor-mediated antiviral signaling. EMBO Rep, 17, 1155-1168.

    61. Wang, Z., Tuo, X., Zhang, J., Chai, K., Tan, J.,Qiao, W., 2022. Antiviral role of IFITM3 in prototype foamy virus infection. Virol J, 19, 195.

    62. Ward, A.E., Kiessling, V., Pornillos, O., White, J.M., Ganser-Pornillos, B.K.,Tamm, L.K., 2020. HIV-cell membrane fusion intermediates are restricted by Serincs as revealed by cryo-electron and TIRF microscopy. J Biol Chem, 295, 15183-15195.

    63. Wilk, T., Geiselhart, V., Frech, M., Fuller, S.D., Flugel, R.M.,Lochelt, M., 2001. Specific interaction of a novel foamy virus Env leader protein with the N-terminal Gag domain. J Virol, 75, 7995-8007.

    64. Xiong, M.G., Xu, Z.S., Li, Y.H., Wang, S.Y., Wang, Y.Y.,Ran, Y., 2020. RNF152 positively regulates TLR/IL-1R signaling by enhancing MyD88 oligomerization. EMBO Rep, 21, e48860.

    65. Xu, F., Tan, J., Liu, R., Xu, D., Li, Y., Geng, Y., Liang, C.,Qiao, W., 2011. Tetherin inhibits prototypic foamy virus release. Virol J, 8, 198.

    66. Xu F, X.D., Li S, Wang M, Qiao W, 2011. A quantitative assay for measuring of prototypic foamy virus using a luciferase-based indicator cell line. Acta Scientiarum Naturalium Universitatis Nankaiensis, 44, 80-84.

    67. Yan, J., Zheng, Y., Yuan, P., Wang, S., Han, S., Yin, J., Peng, B., Li, Z., Sun, Y., He, X.,Liu, W., 2021. Novel Host Protein TBC1D16, a GTPase Activating Protein of Rab5C, Inhibits Prototype Foamy Virus Replication. Front Immunol, 12, 658660.

    68. Yang, Y., Wang, S.Y., Huang, Z.F., Zou, H.M., Yan, B.R., Luo, W.W.,Wang, Y.Y., 2016. The RNA-binding protein Mex3B is a coreceptor of Toll-like receptor 3 in innate antiviral response. Cell Res, 26, 288-303.

    69. Yang, Y.H., Wen, R., Yang, N., Zhang, T.N.,Liu, C.F., 2023. Roles of protein post-translational modifications in glucose and lipid metabolism: mechanisms and perspectives. Mol Med, 29, 93.

    70. Yau, R.,Rape, M., 2016. The increasing complexity of the ubiquitin code. Nat Cell Biol, 18, 579-586.

    71. Yoon, G.H., Kim, K., Park, D.S.,Choi, S.C., 2022. RNF152 negatively regulates Wnt/β-catenin signaling in Xenopus embryos. BMB Rep, 55, 232-237.

    72. York, A., Kutluay, S.B., Errando, M.,Bieniasz, P.D., 2016. The RNA Binding Specificity of Human APOBEC3 Proteins Resembles That of HIV-1 Nucleocapsid. PLoS Pathog, 12, e1005833.

    73. Yu, A., Skorupka, K.A., Pak, A.J., Ganser-Pornillos, B.K., Pornillos, O.,Voth, G.A., 2020. TRIM5α self-assembly and compartmentalization of the HIV-1 viral capsid. Nat Commun, 11, 1307.

    74. Yuan, P., Yan, J., Wang, S., Guo, Y., Xi, X., Han, S., Yin, J., Peng, B., He, X., Bodem, J.,Liu, W., 2021. Trim28 acts as restriction factor of prototype foamy virus replication by modulating H3K9me3 marks and destabilizing the viral transactivator Tas. Retrovirology, 18, 38.

    75. Yuan, Z., Hu, B., Xiao, H., Tan, X., Li, Y., Tang, K., Zhang, Y., Cai, K.,Ding, B., 2021. The E3 Ubiquitin Ligase RNF5 Facilitates SARS-CoV-2 Membrane Protein-Mediated Virion Release. mBio, 13, e0316821.

    76. Yurkovetskiy, L., Guney, M.H., Kim, K., Goh, S.L., Mccauley, S., Dauphin, A., Diehl, W.E.,Luban, J., 2018. Primate immunodeficiency virus proteins Vpx and Vpr counteract transcriptional repression of proviruses by the HUSH complex. Nat Microbiol, 3, 1354-1361.

    77. Zhang, J., Han, C., Xiong, Z., Qiu, M., Tuo, X., Wang, C., Qiao, W.,Tan, J., 2022. SGK1, a Serine/Threonine Kinase, Inhibits Prototype Foamy Virus Replication. Microbiol Spectr, 10, e0199521.

    78. Zhang, J., Wang, C., Tuo, X., Chai, K., Xu, Y., Qiao, W.,Tan, J., 2020. Prototype foamy virus downregulates RelB expression to facilitate viral replication. FEBS Open Bio, 10, 2137-2148.

    79. Zhu, D., Nie, Y., Zhao, Y., Chen, X., Yang, Z.,Yang, Y., 2023. RNF152 Suppresses Fatty Acid Oxidation and Metastasis of Lung Adenocarcinoma by Inhibiting IRAK1-Mediated AKR1B10 Expression. Am J Pathol, 193, 1603-1617.

  • 加载中

Figures(1)

Article Metrics

Article views(19) PDF downloads(0) Cited by()

Related
Proportional views

    RNF152 regulates prototype foamy virus replication by targeting Gag polyubiquitination and VLPs production

      Corresponding author: Wentao Qiao, wentaoqiao@nankai.edu.cn
      Corresponding author: Juan Tan, juantan@nankai.edu.cn
    • Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China

    Abstract: Prototype foamy viruses (PFVs) are complex retroviruses that establish long-term latent infections in hosts without causing disease, positioning them as potential safe gene transfer vectors. Understanding the host proteins involved in PFV replication and their interaction mechanisms may enhance gene transfer efficiency. However, only a few cellular proteins are known to influence PFV replication. Based on the transcriptomic analysis of PFV-infected HT1080 cells, we observed a potential significance of RING finger protein 152 (RNF152) in modulating PFV replication. Overexpression of RNF152 significantly inhibits PFV replication, whereas RNF152 knockdown enhances viral replication. Mechanistically, RNF152 interacts with the Gag protein to promote its polyubiquitination at lysine 396 (K396), thereby facilitating its degradation via the ubiquitin-proteasome system. Furthermore, RNF152 reduces the size and number of PFV virus-like particles (VLPs) by inhibiting the multimerization of Gag. Collectively, our findings reveal a previously unrecognized mechanism that influences PFV infection. Additionally, we elucidate the role of RNF152 in affecting virus replication for the first time, providing valuable insights into the mechanisms of virus replication and demonstrating the importance of ubiquitination modification in affecting viral replication.

    Figure (1)  Reference (79) Relative (20)

    目录

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return