Abstract
Viruses can be engineered for oncolysis, gene therapy, or vaccines. Oncolytic viruses and viral vector for cell and gene therapies are promising modalities of biopharmaceutical development pipelines, with more than 1000 treatments in clinical trials at the end of 2019. The manufacturing demand for virus-based therapies is projected to increase with about 10–20 cell and gene therapies being approved per year by 2025. Many of these therapies require viral vectors as either key raw materials or the therapeutics themselves. Developing and manufacturing viral vectors require an appreciation of virology, cell biology, and a comprehensive understanding of immune responses to infection to produce high-quality, safe, efficacious, and economically viable treatments. The chapter discusses key scientific concepts focusing on the nature of enveloped and non-enveloped viruses, their replication cycles, and innate immune responses as a consequence of virus–host interactions.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ahmad I, Wilson DW (2020) HSV-1 cytoplasmic envelopment and egress. Int J Mol Sci 21:5969
Amara A, Mercer J (2015) Viral apoptotic mimicry. Nat Rev Microbiol 13:461–469
Bergelson JM, Coyne CB (2013) Viral entry into host cells. Adv Exp Med Biol 790:24–41
Bommareddy PK, Shettigar M, Kaufman HL (2018) Integrating oncolytic viruses in combination cancer immunotherapy. Nat Rev Immunol 18:498–513
Casjens S, King J (1975) Virus assembly. Annu Rev Biochem 44:555–611
Castro IF, Volonté L, Risco C (2013) Biogenesis and architecture of virus factories. Cell Microbiol 15:24–34
Chen PH, Ornelles DA, Shenk T (1993) The adenovirus L3 23-kilodalton proteinase cleaves the amino-terminal head domain from cytokeratin 18 and disrupts the cytokeratin network of HeLa cells. J Virol 67:3507–3514
Chiou SK, Tseng CC, Rao L, White E (1994) Functional complementation of the adenovirus E1B 19-kilodalton protein with Bcl-2 in the inhibition of apoptosis in infected cells. J Virol 68:6553–6566
Chiramel AI, Brady NR, Bartenschlager R (2013) Divergent roles of autophagy in virus infection. Cells 2:83–104
Chung YH, Cai H, Steinmetz NF (2020) Viral nanoparticles for drug delivery, imaging, immunotherapy, and theranostic applications. Adv Drug Deliver Rev 156:214–235
Cook KC, Cristea IM (2019) Location is everything: protein translocations as a viral infection strategy. Curr Opin Chem Biol 48:34–43
Croft SN, Walker EJ, Ghildyal R (2017) Picornaviruses and apoptosis: subversion of cell death. Mbio 8:e01009–e01017
Crump C (2018) Human herpesviruses. Adv Exp Med Biol 1045:23–44
Daugherty MD, Malik HS (2012) Rules of engagement: molecular insights from host-virus arms races. Annu Rev Genet 46:677–700
de Pablo PJ, Martín CS (2022) Seeing and touching adenovirus: complementary approaches for understanding assembly and disassembly of a complex virion. Curr Opin Virol 52:112–122
Deretic V (2021) Autophagy in inflammation, infection, and immunometabolism. Immunity 54:437–453
Dimitrov DS (2000) Cell biology of virus entry. Cell 101:697–702
Earley LF et al (2017) Adeno-associated virus (AAV) assembly-activating protein is not an essential requirement for capsid assembly of AAV serotypes 4, 5, and 11. J Virol 91
Elmore ZC et al (2021) The membrane associated accessory protein is an adeno-associated viral egress factor. Nat Commun 12:6239
Ficarelli M, Neil SJD, Swanson CM (2021) Targeted restriction of viral gene expression and replication by the ZAP antiviral system. Ann Rev Virol 8:1–19
Formas-Oliveira AS, Basílio JS, Rodrigues AF, Coroadinha AS (2020) Overexpression of ER protein processing and apoptosis regulator genes in human embryonic kidney 293 cells improves gene therapy vectors production. Biotechnol J 15:1900562
Gaudin Y (2021) Penetration of non-enveloped viruses. Nat Microbiol 6:1343–1344
Georgi F, Greber UF (2020) The Adenovirus Death Protein – a small membrane protein controls cell lysis and disease. FEBS Lett 594:1861–1878
Gerlier D, Varior-Krishnan G, Devaux P (1995) CD46-mediated measles virus entry: a first key to host-range specificity. Trends Microbiol 3:338–345
Ghigo E (2010) A dilemma for viruses and giant viruses: which endocytic pathway to use to enter cells? Intervirology 53:274–283
Greber UF, Flatt JW (2019) Adenovirus entry: from infection to immunity. Ann Rev Virol 6:1–21
Haan PD, Diemen FRV, Toscano MG (2020) Viral gene delivery vectors: the next generation medicines for immune-related diseases. Hum Vacc Immunother 17:1–8
Haller O, Staeheli P, Kochs G (2007) Interferon-induced Mx proteins in antiviral host defense. Biochimie 89:812–818
Hanson HM, Willkomm NA, Yang H, Mansky LM (2022) Human retrovirus genomic RNA packaging. Viruses 14:1094
Harrison SC (2015) Viral membrane fusion. Virology 479:498–507
Iwasaki A, Medzhitov R (2015) Control of adaptive immunity by the innate immune system. Nat Immunol 16:343–353
Kerviel A, Zhang M, Altan-Bonnet N (2021) A new infectious unit: extracellular vesicles carrying virus populations. Annu Rev Cell Dev Bi 37:1–27
Kit S (1979) Viral-associated and induced enzymes. Pharmacol Therapeut 4:501–585
Koonin EV, Dolja VV, Krupovic M (2022) The logic of virus evolution. Cell Host Microbe 30:917–929
Krebs A-S, Mendonça LM, Zhang P (2021) Structural analysis of retrovirus assembly and maturation. Viruses 14:54
Letarov AV (2020) History of early bacteriophage research and emergence of key concepts in virology. Biochem Mosc 85:1093–1112
Liu BC, Sarhan J, Poltorak A (2018) Host-intrinsic interferon status in infection and immunity. Trends Mol Med 24:658–668
Lucic B, de Castro IJ, Lusic M (2021) Viruses in the nucleus. CSH Perspect Biol 13:a039446
Luque D, Castón JR (2020) Cryo-electron microscopy for the study of virus assembly. Nat Chem Biol 16:231–239
Maertens GN, Engelman AN, Cherepanov P (2022) Structure and function of retroviral integrase. Nat Rev Microbiol 20:20–34
McCann N, Castellino FJ (2022) Cell entry and unusual replication of SARS-CoV-2. Curr Drug Targets 23:1539–1554
Mercer J, Schelhaas M, Helenius A (2010) Virus entry by endocytosis. Annu Rev Biochem 79:803–833
Moaven O, Mangieri CW, Stauffer JA, Anastasiadis PZ, Borad MJ (2021) Strategies to develop potent oncolytic viruses and enhance their therapeutic efficacy. JCO Precis Oncol 5:733–743
Moller-Tank S, Maury W (2014) Phosphatidylserine receptors: enhancers of enveloped virus entry and infection. Virology 468:565–580
Morran LT, Schmidt OG, Gelarden IA, Parrish RC II, Lively CM (2011) Running with the Red Queen: host-parasite coevolution selects for biparental sex. Science 333:216–218
Moss B (2013) Poxvirus DNA replication. CSH Perspect Biol 5:a010199
Neil SJD (2013) Intrinsic immunity. Curr Top Microbiol 371:67–104
Netherton CL, Wileman T (2011) Virus factories, double membrane vesicles and viroplasm generated in animal cells. Curr Opin Virol 1:381–387
Nóbrega C, Mendonça L, Matos CA (2020) A handbook of gene and cell therapy. Springer, pp 39–90. https://doi.org/10.1007/978-3-030-41333-0_3
Nonnenmacher M, Weber T (2011) Adeno-associated virus 2 infection requires endocytosis through the CLIC/GEEC pathway. Cell Host Microbe 10:563–576
Owen DJ, Crump CM, Graham SC (2015) Tegument assembly and secondary envelopment of alphaherpesviruses. Viruses 7:5084–5114
Pais DAM, Portela RMC, Carrondo MJT, Isidro IA, Alves PM (2019) Enabling PAT in insect cell bioprocesses: in situ monitoring of recombinant adeno-associated virus production by fluorescence spectroscopy. Biotechnol Bioeng 116:2803–2814
Perry C, Rayat ACME (2021) Lentiviral vector bioprocessing. Viruses 13:268
Pillay S, Carette JE (2017) Host determinants of adeno-associated viral vector entry. Curr Opin Virol 24:124–131
Pornillos O, Ganser-Pornillos BK (2019) Maturation of retroviruses. Curr Opin Virol 36:47–55
Romero-Brey I, Bartenschlager R (2016) Endoplasmic reticulum: the favorite intracellular niche for viral replication and assembly. Viruses 8:160
Sadeghpour S, Khodaee S, Rahnama M, Rahimi H, Ebrahimi D (2021) Human APOBEC3 variations and viral infection. Viruses 13:1366
Schmid M, Speiseder T, Dobner T, Gonzalez RA (2014) DNA virus replication compartments. J Virol 88:1404–1420
Schoggins JW (2019) Interferon-stimulated genes: what do they all do? Ann Rev Virol 6:1–18
Sonntag F, Schmidt K, Kleinschmidt JA (2010) A viral assembly factor promotes AAV2 capsid formation in the nucleolus. Proc Natl Acad Sci 107:10220–10225
Strotz LC et al (2018) Getting somewhere with the Red Queen: chasing a biologically modern definition of the hypothesis. Biol Lett 14:20170734
Tsu BV et al (2021) Running with scissors: evolutionary conflicts between viral proteases and the host immune system. Front Immunol 12:769543
van Gent M, Sparrer KMJ, Gack MU (2018) TRIM proteins and their roles in antiviral host defenses. Ann Rev Virol 5:385–405
Velthuis AJW, Grimes JM, Fodor E (2021) Structural insights into RNA polymerases of negative-sense RNA viruses. Nat Rev Microbiol 19:303–318
Votteler J, Sundquist WI (2013) Virus budding and the ESCRT pathway. Cell Host Microbe 14:232–241
Wolff G, Bárcena M (2021) Multiscale electron microscopy for the study of viral replication organelles. Viruses 13:197
Yan N, Chen ZJ (2012) Intrinsic antiviral immunity. Nat Immunol 13:214–222
Zhao J et al (2010) Cytomegalovirus β2.7 RNA transcript protects endothelial cells against apoptosis during ischemia/reperfusion injury. J Hear Lung Transplant 29:342–345
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this chapter
Cite this chapter
Chiramel, A.I., Kissinger, R., Gorr, I.H. (2023). An Overview of the Cell Biology and Genetic Barriers to Virus Infections with Implications in Cell Line Development for Virotherapy. In: Gautam, S., Chiramel, A.I., Pach, R. (eds) Bioprocess and Analytics Development for Virus-based Advanced Therapeutics and Medicinal Products (ATMPs). Springer, Cham. https://doi.org/10.1007/978-3-031-28489-2_4
Download citation
DOI: https://doi.org/10.1007/978-3-031-28489-2_4
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-031-28488-5
Online ISBN: 978-3-031-28489-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)