journal article·2024-01Open access

Navigating Latency-Inducing Viral Infections: Therapeutic Targeting and Nanoparticle Utilization

Arathy Vasukutty, Yeonwoo Jang, Dongwan Han, Hansoo Park, In-Kyu Park

Abstract

The investigation into viral latency illuminates its pivotal role in the survival strategies of diverse viruses, including herpesviruses, HIV, and HPV. This underscores the delicate balance between dormancy and the potential for reactivation. The study explores the intricate mechanisms governing viral latency, encompassing episomal and proviral forms, and their integration with the host’s genetic material. This integration provides resilience against cellular defenses, substantially impacting the host–pathogen dynamic, especially in the context of HIV, with implications for clinical outcomes. Addressing the challenge of eradicating latent reservoirs, this review underscores the potential of epigenetic and genetic interventions. It highlights the use of innovative nanocarriers like nanoparticles and liposomes for delivering latency-reversing agents. The precision in delivery, capacity to navigate biological barriers, and sustained drug release by these nanocarriers present a promising strategy to enhance therapeutic efficacy. The review further explores nanotechnology's integration in combating latent viral infections, leveraging nanoparticle-based platforms for drug delivery, gene editing, and vaccination. Advances in lipid-based nanocarriers, polymeric nanoparticles, and inorganic nanoparticles are discussed, illustrating their potential for targeted, efficient, and multifunctional antiviral therapy. By merging a deep understanding of viral latency’s molecular underpinnings with nanotechnology’s transformative capabilities, this review underscores the promise of novel therapeutic interventions. These interventions have great potential for managing persistent viral infections, heralding a new era in the fight against diseases such as neuroHIV/AIDS, herpes, and HPV.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: RNA Interference and Gene Delivery · Immunotherapy and Immune Responses · SARS-CoV-2 and COVID-19 Research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Biomedical Sciences and BioMedical Sciences Graduate Program (BMSGP), Chonnam National University Medical School, Jeollanam-do 58128, Republic of Korea.

School of Integrative Engineering, Chung-Ang University, Seoul 06974, Republic of Korea.

Funding

Korea Institute for Advanced Study

References (100+)

Show source-provided references
1. 10.1016/j.chom.2010.06.01410.1016/j.chom.2010.06.014 ↗
2. 10.2217/fvl.11.2110.2217/fvl.11.21 ↗
3. 10.1016/j.chom.2016.04.00810.1016/j.chom.2016.04.008 ↗
4. Rampersad S, Tennant P. Replication and expression strategies of viruses. Viruses. 2018;55–82.
5. Domingo E. Trends in antiviral strategies. Virus Populat. 2020;301–339.10.1016/B978-0-12-816331-3.00009-X ↗
6. Siliciano RF, Greece WC. HIV latency. Cold Spring Harb Perspect Med. 2011;1(1): Article a007096.10.1101/cshperspect.a007096 ↗
7. Dufour C, Gantner P, Fromentin R, Chormont N. The multifaceted nature of HIV latency. J Clin Invest. 2021;130(7):3381–3390.10.1172/JCI136227 ↗
8. Jütte BB, Love L, Svensson JP. Molecular mechanisms of HIV-1 latency from a chromatin and epigenetic perspective. Curr Clin Microbiol Rep. 2023;10(4):246–254.10.1007/s40588-023-00208-3 ↗
9. 10.1186/s13148-015-0137-610.1186/s13148-015-0137-6 ↗
10. Kumar M, Haque SI, Kishore N, Kumar S. A comparison of efficacy of valacyclovir and famciclovir in herpes zoster in the eastern Indian population. J Cardiovasc Dis Res. 2022;13(4):762–766.
11. 10.1038/s41579-020-0382-310.1038/s41579-020-0382-3 ↗
12. Donahue DA, Wainberg MA. Cellular and molecular mechanisms involved in the establishment of HIV-1 latency. Retrovirology. 2013;10:11.10.1186/1742-4690-10-11 ↗
13. Abdel-Hameed EA, Ji H, Shata MT. HIV-induced epigenetic alterations in host cells. Adv Exp Med Biol. 2016;879:27–38.10.1007/978-3-319-24738-0_2 ↗
14. Nehme Z, Pasquereau S, Herbein G. Control of viral infections by epigenetic-targeted therapy. Clin Epigenetics. 2019;11:55.10.1186/s13148-019-0654-9 ↗
15. De Monte A, Courjon J, Anty R, Cua E, Naqvi A, Mondain V, Cottalorda J, Ollier L, Giordanengo V. Direct-acting antiviral treatment in adults infected with hepatitis C virus: Reactivation of hepatitis B virus coinfection as a further challenge. J Clin Virol. 2016;78:27–30.10.1016/j.jcv.2016.02.026 ↗
16. Johnston C, Gottlieb SL, Wald A. Status of vaccine research and development of vaccines for herpes simplex virus. Vaccine. 2016;34(26):2948–2952.10.1016/j.vaccine.2015.12.076 ↗
17. 10.1080/15384101.2018.144262310.1080/15384101.2018.1442623 ↗
18. 10.3390/v1004015710.3390/v10040157 ↗
19. 10.1166/jbn.2021.307410.1166/jbn.2021.3074 ↗
20. Zhou J, Krishnan N, Jiang Y, Fang RH, Zhang L. Nanotechnology for virus treatment. Nano Today. 2021;36: Article 101031.10.1016/j.nantod.2020.101031 ↗
21. Pradhan D, Biswasroy P, Goyal A, Ghosh G, Rath G. Recent advancement in nanotechnology-based drug delivery system against viral infections. AAPS PharmSciTech. 2021;22:47.10.1208/s12249-020-01908-5 ↗
22. M AS, Wadhwani A. Novel applications of nanotechnology in controlling HIV and HSV infections. Curr Drug Res Rev. 2021;13(2):120–129.10.2174/2589977512999201124121931 ↗
23. Soundararajan D, Ramana LN, Shankaran P, Krishnan UM. Nanoparticle-based strategies to target HIV-infected cells. Colloids Surf B Biointerfaces. 2022;213: Article 112405.10.1016/j.colsurfb.2022.112405 ↗
24. Maus A, Strait L, Zhu D. Nanoparticles as delivery vehicles for antiviral therapeutic drugs. Eng Regen. 2021;2:31–46.
25. Perales SG Rajasingh S Zhou Z Rajasingh J. Therapy of infectious diseases using epigenetic approaches. Epigenet Hum Dis. 2024:853–882.10.1016/B978-0-443-21863-7.00007-X ↗
26. Niller HH Minarovits J Epigenetics and human infectious diseases. Epigenet Hum Dis. 2024:779–852.10.1016/B978-0-443-21863-7.00006-8 ↗
27. Fischer N. Infection-induced epigenetic changes and their impact on the pathogenesis of diseases. Semin Immunopathol. 2020;42(2):127–130.10.1007/s00281-020-00793-1 ↗
28. Mbonye U, Karn J. Transcriptional control of HIV latency: Cellular signaling pathways, epigenetics, happenstance and the hope for a cure. Virology. 2014;454:328–339.10.1016/j.virol.2014.02.008 ↗
29. Turner A-MW, Margolis DM. Chromatin regulation and the histone code in HIV latency. Yale J Biol Med. 2017;90(2):229–243.
30. 10.1016/j.tim.2013.02.00510.1016/j.tim.2013.02.005 ↗
31. Cliffe AR, Coen DM, Knipe DM. Kinetics of facultative heterochromatin and polycomb group protein association with the herpes simplex viral genome during establishment of latent infection. mBio. 2013;4(1): Article e00590-12.10.1128/mBio.00590-12 ↗
32. Cliffe AR, Garber DA, Knipe DM. Transcription of the herpes simplex virus latency-associated transcript promotes the formation of facultative heterochromatin on lytic promoters. J Virol. 2009;83(16):8182–8190.10.1128/JVI.00712-09 ↗
33. 10.15252/embj.20159132010.15252/embj.201591320 ↗
34. 10.1038/ncomms686810.1038/ncomms6868 ↗
35. Lu F, Zankharia U, Vladimirova O, Yi Y, Collman RG, Lieberman PM. Epigenetic landscape of HIV-1 infection in primary human macrophage. J Virol. 2022;96(7):e00162-22.10.1128/jvi.00162-22 ↗
36. Margolos DM. Histone deacetylase inhibitors and HIV latency. Curr Opin HIV AIDS. 2011;6(1):25.10.1097/COH.0b013e328341242d ↗
37. Youssoufian H, Hammer SM, Hirsch MS, Mulder C. Methylation of the viral genome in an in vitro model of herpes simplex virus latency. Proc Natl Acad Sci USA. 1982;79(7):2207–2210.10.1073/pnas.79.7.2207 ↗
38. Bednarik DP, Cook J, Pitha PM. Inactivation of the HIV LTR by DNA CpG methylation: Evidence for a role in latency. EMBO J. 1990;9(4):1157–1164.10.1002/j.1460-2075.1990.tb08222.x ↗
39. Schaefer BC, Strominger JL, Speck SH. Host-cell-determined methylation of specific Epstein-Barr virus promoters regulates the choice between distinct viral latency programs. Mol Cell Biol. 1997;17(1):364–377.10.1128/MCB.17.1.364 ↗
40. Flower K, Thomas D, Heather J, Ramasubramanyan S, Jones S, Sinclair AJ. Epigenetic control of viral life-cycle by a DNA-methylation dependent transcription factor. PLOS ONE. 2011;6(10): Article e25922.10.1371/journal.pone.0025922 ↗
41. 10.1172/JCI13622510.1172/JCI136225 ↗
42. Verma M. Viral genes and methylation. Ann N Y Acad Sci. 2003;983(1):170–180.10.1111/j.1749-6632.2003.tb05972.x ↗
43. Mantovani N, Defelicibus A, da Silva IT, Cicero MF, Santana LC, Arnold R, de Castro DF, Duro RLS, Nishiyama-Jr MY, de Azevedo ILMJ, et al. Latency-associated DNA methylation patterns among HIV-1 infected individuals with distinct disease progression courses or antiretroviral virologic response. Sci Rep. 2021;11(1):22993.10.1038/s41598-021-02463-0 ↗
44. G.S. Hailu Design synthesis and biological evaluation of novel epigenetic modulators for parasitic diseases. 2017.
45. Cheray M, Pacaud R, Hervouet E, Vallette FM, Cartron P-F. DNMT inhibitors in cancer, current treatments and future promising approach: Inhibition of specific DNMT-including complexes. Epigenet Diagn Ther. 2015;1(1):37–48.10.2174/2214083201666150221002056 ↗
46. Zahnow C, Topper M, Stone M, Murray-Stewart T, Li H, Baylin S, Casero R Jr. Inhibitors of DNA methylation, histone deacetylation, and histone demethylation: A perfect combination for cancer therapy. Adv Cancer Res. 2016;130:55–111.10.1016/bs.acr.2016.01.007 ↗
47. Seem K, Kaur S, Kumar S, Mohapatra T. Epigenome editing for targeted DNA (de) methylation: A new perspective in modulating gene expression. Crit Rev Biochem Mol Biol. 2024;59(1-2):69–98.10.1080/10409238.2024.2320659 ↗
48. Knipe DM, Lieberman PM, Jung JU, McBride AA, Morris KV, Ott M, Margolis D, Nieto A, Nevels M, Parks RJ, et al. Snapshots: Chromatin control of viral infection. Virology. 2013;435(1):141–156.10.1016/j.virol.2012.09.023 ↗
49. Reeves M, MacAry P, Lehner P, Sissons J, Sinclair JH. Latency, chromatin remodeling, and reactivation of human cytomegalovirus in the dendritic cells of healthy carriers. Proc Natl Acad Sci USA. 2005;102(11):4140–4145.10.1073/pnas.0408994102 ↗
50. Li C, Mousseau G, Valente ST. Tat inhibition by didehydro-Cortistatin A promotes heterochromatin formation at the HIV-1 long terminal repeat. Epigenetics Chromatin. 2019;12(1):23.10.1186/s13072-019-0267-8 ↗
51. 10.1038/nrm.2017.9410.1038/nrm.2017.94 ↗
52. Vasukutty A, Pillarisetti S, Choi J, Kang SH, Park I-K. CXCR4 targeting nanoplatform for transcriptional activation of latent HIV-1 infected T cells. ACS Appl Bio Mater. 2024;7(8):4831–4842.10.1021/acsabm.3c00456 ↗
53. Lum KK-Y. Integrating virology and proteomics to comprehend mechanisms of innate immune signaling during herpesvirus infection [thesis]. [Princeton (NJ)]: Princeton University; 2019.
54. Saha S. Histone modifications and other facets of epigenetic regulation in trypanosomatids: Leaving their mark. mBio. 2020;11(5): Article e01079-20.10.1128/mBio.01079-20 ↗
55. Sahu RK, Singh S, Tomar RS. The mechanisms of action of chromatin remodelers and implications in development and disease. Biochem Pharmacol. 2020;180: Article 114200.10.1016/j.bcp.2020.114200 ↗
56. 10.3390/v1205052910.3390/v12050529 ↗
57. 10.1016/j.virol.2017.03.00210.1016/j.virol.2017.03.002 ↗
58. 10.1093/nar/gkz11710.1093/nar/gkz117 ↗
59. Park K. Nanotechnology: What it can do for drug delivery. J Control Release. 2007;120(1-2):1–3.10.1016/j.jconrel.2007.05.003 ↗
60. 10.1039/c2cs15327k10.1039/c2cs15327k ↗
61. Samimi S Maghsoudnia N Eftekhari RB Dorkoosh F. Lipid-based nanoparticles for drug delivery systems. In: Characterization and biology of nanomaterials for drug delivery. Amsterdam (Netherlands): Elsevier; 2019. p. 47–76.10.1016/B978-0-12-814031-4.00003-9 ↗
62. 10.1208/s12248-015-9780-210.1208/s12248-015-9780-2 ↗
63. Jang Y, Kim A, Moon JJ, Lee JY, Park H. Novel bioengineering strategies for drug delivery systems, applied. Mater Today. 2023;33: Article 101834.
64. Faria MJ, Lopes CM, das Neves J, Lúcio M. Lipid nanocarriers for anti-HIV therapeutics: A focus on physicochemical properties and biotechnological advances. Pharmaceutics. 2021;13(8):1294.10.3390/pharmaceutics13081294 ↗
65. Mertz GJ, Jones CC, Mills J, Fife KH, Lemon SM, Stapleton JT, Hill EL, Davis LG. Long-term acyclovir suppression of frequently recurring genital herpes simplex virus infection: A multicenter double-blind trial. JAMA. 1988;260(2):201–206.10.1001/jama.1988.03410020067030 ↗
66. Gupta R, Wald A, Krantz E, Selke S, Warren T, Vargas-Cortes M, Miller G, Corey L. Valacyclovir and acyclovir for suppression of shedding of herpes simplex virus in the genital tract. J Infect Dis. 2004;190(8):1374–1381.10.1086/424519 ↗
67. 10.1016/j.coviro.2016.09.01210.1016/j.coviro.2016.09.012 ↗
68. 10.1021/acsinfecdis.7b0027310.1021/acsinfecdis.7b00273 ↗
69. Grosse S, Huot N, Mahiet C, Arnould S, Barradeau S, Le Clerre D, Chion-Sotinel I, Jacqmarcq C, Chapellier B, Ergani AJMT, et al. Meganuclease-mediated inhibition of HSV1 infection in cultured cells. Mol Ther. 2011;19(4):694–702.10.1038/mt.2010.302 ↗
70. 10.1093/nar/gkt57110.1093/nar/gkt571 ↗
71. 10.1093/nar/gku30510.1093/nar/gku305 ↗
72. 10.1007/s11427-021-2057-010.1007/s11427-021-2057-0 ↗
73. Aubert M, Strongin DE, Roychoudhury P, Loprieno MA, Haick AK, Klouser LM, Stensland L, Huang M-L, Makhsous N, Tait A. Gene editing and elimination of latent herpes simplex virus in vivo. Nat Commun. 2020;11(1):4148.10.1038/s41467-020-17936-5 ↗
74. Badia R, Ballana E, Esté JA, Riveira-Muñoz E. Antiviral treatment strategies based on gene silencing and genome editing. Curr Opin Virol. 2017;24:46–54.10.1016/j.coviro.2017.04.001 ↗
75. 10.3390/vaccines1011194610.3390/vaccines10111946 ↗
76. Chattopadhyay S, Chen J-Y, Chen H-W, Hu C-MJ. Nanoparticle vaccines adopting virus-like features for enhanced immune potentiation. Nano. 2017;1(3):244–260.
77. 10.1016/j.addr.2021.01.00210.1016/j.addr.2021.01.002 ↗
78. Nasrollahzadeh M, Sajjadi M, Soufi GJ, Iravani S, Varma RS. Nanomaterials and nanotechnology-associated innovations against viral infections with a focus on coronaviruses. Nano. 2020;10(6):1072.
79. Bowen A, Sweeney EE, Fernandes R. Nanoparticle-based immunoengineered approaches for combating HIV. Front Immunol. 2020;11:789.10.3389/fimmu.2020.00789 ↗
80. Fredriksen BN, Grip J. PLGA/PLA micro-and nanoparticle formulations serve as antigen depots and induce elevated humoral responses after immunization of Atlantic salmon (Salmo salar L.). Vaccine. 2012;30(3):656–667.10.1016/j.vaccine.2011.10.105 ↗
81. Gregory AE, Titball R, Williamson D. Vaccine delivery using nanoparticles. Front Cell Infect Microbiol. 2013;3:13.10.3389/fcimb.2013.00013 ↗
82. Tang X, Liang Y, Liu X, Zhou S, Liu L, Zhang F, Xie C, Cai S, Wei J, Zhu Y, et al. PLGA-PEG nanoparticles coated with anti-CD45RO and loaded with HDAC plus protease inhibitors activate latent HIV and inhibit viral spread. Nanoscale Res Lett. 2015;10(1):413.10.1186/s11671-015-1112-z ↗
83. Hong J, Choi Y, Lee G, Kim J, Jang Y, Yoon CH, Seo HW, Park IK, Kang SH, Choi J. Nanosome-mediated delivery of HDAC inhibitors and oxygen molecules for the transcriptional reactivation of latent HIV-infected CD4+ T cells. Small. 2023;19(37):e2301730.10.1002/smll.202301730 ↗
84. Shrivastava S, Ray RM, Holguin L, Echavarria L, Grepo N, Scott TA, Burnett J, Morris KV. Exosome-mediated stable epigenetic repression of HIV-1. Nat Commun. 2021;12(1):5541.10.1038/s41467-021-25839-2 ↗
85. 10.1007/s12033-021-00334-710.1007/s12033-021-00334-7 ↗
86. Akpamagbo YA, DeMarino C, Pleet ML, Schwab A, Rodriguez M, Barclay RA, Sampey G, Iordanskiy S, El-Hage N, Kashanchi F. HIV-1 transcription inhibitors increase the synthesis of viral non-coding RNA that contribute to latency. Curr Pharm Des. 2017;23(28):4133–4144.10.2174/1381612823666170622101319 ↗
87. Royo-Rubio E, Rodríguez-Izquierdo I, Moreno-Domene M, Lozano-Cruz T, de la Mata F, Gómez R, Muñoz-Fernández M, Jiménez J. Promising PEGylated cationic dendrimers for delivery of miRNAs as a possible therapy against HIV-1 infection. J Nanobiotechnol. 2021;19(1):158.10.1186/s12951-021-00899-0 ↗
88. Désormeaux A, Bergeron MG. Liposomes as drug delivery system: A strategic approach for the treatment of HIV infection. J Drug Target. 1998;6(1):1–15.10.3109/10611869808997877 ↗
89. Wu D, Si M, Xue HY, Tran NT, Khalili K, Kaminski R, Wong HL. Lipid nanocarrier targeting activated macrophages for antiretroviral therapy of HIV reservoir. Nanomedicine. 2023;18(20):1343–1360.10.2217/nnm-2023-0120 ↗
90. Bestman-Smith J, Désormeaux A, Tremblay MJ, Bergeron MG. Targeting cell-free HIV and virally-infected cells with anti-HLA-DR immunoliposomes containing amphotericin B. AIDS. 2000;14(16):2457–2465.10.1097/00002030-200011100-00006 ↗
91. Hamilton JR, Chen E, Perez BS, Sandoval Espinoza CR, Kang MH, Trinidad M, Ngo W, Doudna JA. In vivo human T cell engineering with enveloped delivery vehicles. Nat Biotechnol. 2024.10.1038/s41587-023-02085-z ↗
92. 10.1016/j.jconrel.2020.12.03110.1016/j.jconrel.2020.12.031 ↗
93. C.M. Lopes J. Silva M.E.C.R. Oliveira M. Lúcio Lipid-based colloidal carriers for topical application of antiviral drugs. In: Design of nanostructures for versatile therapeutic applications. Oxford (UK): Elsevier; 2018. p. 565–622.10.1016/B978-0-12-813667-6.00014-0 ↗
94. 10.1016/j.ejpb.2016.12.02910.1016/j.ejpb.2016.12.029 ↗
95. Pei J, Tian Y, Ye W, Han J, Dang Y, Cheng T, Wang W, Zhao Y, Ye W, Huangfu S, et al. Bioscience, A novel recombinant ORF7-siRNA delivered by flexible nano-liposomes inhibits varicella zoster virus infection. Cell Biosci. 2023;13(1):167.10.1186/s13578-023-01108-1 ↗
96. Figueira TN, Domingues MM, Illien F, Cadima-Couto I, Todorovski T, Andreu D, Sagan S, Castanho MA, Walrant A, Veiga AS. Enfuvirtide-protoporphyrin IX dual-loaded liposomes: In vitro evidence of synergy against HIV-1 entry into cells. ACS Infect Dis. 2019;6(2):224–236.10.1021/acsinfecdis.9b00285 ↗
97. Azarnezhad A, Samadian H, Jaymand M, Sobhani M, Ahmadi A. Toxicological profile of lipid-based nanostructures: Are they considered as completely safe nanocarriers? Crit Rev Toxicol. 2020;50(2):148–176.10.1080/10408444.2020.1719974 ↗
98. Xu L, Wang X, Liu Y, Yang G, Falconer RJ, Zhao C-X. Lipid nanoparticles for drug delivery. Adv Nanobiomed Res. 2022;2(2):2100109.10.1002/anbr.202100109 ↗
99. Albertsen CH, Kulkarni JA, Witzigmann D, Lind M, Petersson K, Simonsen JB. The role of lipid components in lipid nanoparticles for vaccines and gene therapy. Adv Drug Deliv Rev. 2022;188: Article 114416.10.1016/j.addr.2022.114416 ↗
100. 10.1016/j.jconrel.2021.01.01710.1016/j.jconrel.2021.01.017 ↗