Molecular Engineering of Virus Tropism

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Oct 26

PMID 39456875

Authors

Bo He

Belinda Wilson

Shih-Heng Chen

Kedar Sharma

Erica Scappini

Molly Cook

Robert Petrovich

Negin P Martin

Affiliations

Soon will be listed here.

Abstract

Engineered viral vectors designed to deliver genetic material to specific targets offer significant potential for disease treatment, safer vaccine development, and the creation of novel biochemical research tools. Viral tropism, the specificity of a virus for infecting a particular host, is often modified in recombinant viruses to achieve precise delivery, minimize off-target effects, enhance transduction efficiency, and improve safety. Key factors influencing tropism include surface protein interactions between the virus and host-cell, the availability of host-cell machinery for viral replication, and the host immune response. This review explores current strategies for modifying the tropism of recombinant viruses by altering their surface proteins. We provide an overview of recent advancements in targeting non-enveloped viruses (adenovirus and adeno-associated virus) and enveloped viruses (retro/lentivirus, Rabies, Vesicular Stomatitis Virus, and Herpesvirus) to specific cell types. Additionally, we discuss approaches, such as rational design, directed evolution, and in silico and machine learning-based methods, for generating novel AAV variants with the desired tropism and the use of chimeric envelope proteins for pseudotyping enveloped viruses. Finally, we highlight the applications of these advancements and discuss the challenges and future directions in engineering viral tropism.

References

Garoff H, Hewson R, Opstelten D . Virus maturation by budding. Microbiol Mol Biol Rev. 1998; 62(4):1171-90. PMC: 98943. DOI: 10.1128/MMBR.62.4.1171-1190.1998. View

Yang M, Hu C, Lee Y, Chang C, Chen Y, Lee P . Syngeneic mesenchymal stem cells loaded with telomerase-dependent oncolytic adenoviruses enhance anti-metastatic efficacy. Stem Cells Transl Med. 2024; 13(8):738-749. PMC: 11328937. DOI: 10.1093/stcltm/szae039. View

Sakurai K, Zhao S, Takatoh J, Rodriguez E, Lu J, Leavitt A . Capturing and Manipulating Activated Neuronal Ensembles with CANE Delineates a Hypothalamic Social-Fear Circuit. Neuron. 2016; 92(4):739-753. PMC: 5172402. DOI: 10.1016/j.neuron.2016.10.015. View

Schaffer D, Koerber J, Lim K . Molecular engineering of viral gene delivery vehicles. Annu Rev Biomed Eng. 2008; 10:169-94. PMC: 2683887. DOI: 10.1146/annurev.bioeng.10.061807.160514. View

Yao J, Atasheva S, Wagner N, Di Paolo N, Stewart P, Shayakhmetov D . Targeted, safe, and efficient gene delivery to human hematopoietic stem and progenitor cells in vivo using the engineered AVID adenovirus vector platform. Mol Ther. 2023; 32(1):103-123. PMC: 10787117. DOI: 10.1016/j.ymthe.2023.10.023. View

Ferrara F, Del Rosario J, da Costa K, Kinsley R, Scott S, Fereidouni S . Development of Lentiviral Vectors Pseudotyped With Influenza B Hemagglutinins: Application in Vaccine Immunogenicity, mAb Potency, and Sero-Surveillance Studies. Front Immunol. 2021; 12:661379. PMC: 8182064. DOI: 10.3389/fimmu.2021.661379. View

Chen S, Haam J, Walker M, Scappini E, Naughton J, Martin N . Recombinant Viral Vectors as Neuroscience Tools. Curr Protoc Neurosci. 2019; 87(1):e67. PMC: 6438761. DOI: 10.1002/cpns.67. View

Denard J, Rouillon J, Leger T, Garcia C, Lambert M, Griffith G . AAV-8 and AAV-9 Vectors Cooperate with Serum Proteins Differently Than AAV-1 and AAV-6. Mol Ther Methods Clin Dev. 2018; 10:291-302. PMC: 6111067. DOI: 10.1016/j.omtm.2018.08.001. View

Agbandje-Mckenna M, Kleinschmidt J . AAV capsid structure and cell interactions. Methods Mol Biol. 2011; 807:47-92. DOI: 10.1007/978-1-61779-370-7_3. View

10.

Carvalho L, Xiao R, Wassmer S, Langsdorf A, Zinn E, Pacouret S . Synthetic Adeno-Associated Viral Vector Efficiently Targets Mouse and Nonhuman Primate Retina In Vivo. Hum Gene Ther. 2018; 29(7):771-784. PMC: 6066192. DOI: 10.1089/hum.2017.154. View

11.

Garcia-Sastre A . Influenza virus receptor specificity: disease and transmission. Am J Pathol. 2010; 176(4):1584-5. PMC: 2843447. DOI: 10.2353/ajpath.2010.100066. View

12.

Pillay S, Meyer N, Puschnik A, Davulcu O, Diep J, Ishikawa Y . An essential receptor for adeno-associated virus infection. Nature. 2016; 530(7588):108-12. PMC: 4962915. DOI: 10.1038/nature16465. View

13.

Di Paolo N, Miao E, Iwakura Y, Murali-Krishna K, Aderem A, Flavell R . Virus binding to a plasma membrane receptor triggers interleukin-1 alpha-mediated proinflammatory macrophage response in vivo. Immunity. 2009; 31(1):110-21. PMC: 2759279. DOI: 10.1016/j.immuni.2009.04.015. View

14.

Yu H, Koilkonda R, Chou T, Porciatti V, Ozdemir S, Chiodo V . Gene delivery to mitochondria by targeting modified adenoassociated virus suppresses Leber's hereditary optic neuropathy in a mouse model. Proc Natl Acad Sci U S A. 2012; 109(20):E1238-47. PMC: 3356643. DOI: 10.1073/pnas.1119577109. View

15.

Hoffmann M, Zdechlik A, He Y, Nedrud D, Aslanidi G, Gordon W . Multiparametric domain insertional profiling of adeno-associated virus VP1. Mol Ther Methods Clin Dev. 2023; 31:101143. PMC: 10661864. DOI: 10.1016/j.omtm.2023.101143. View

16.

Wang D, Tai P, Gao G . Adeno-associated virus vector as a platform for gene therapy delivery. Nat Rev Drug Discov. 2019; 18(5):358-378. PMC: 6927556. DOI: 10.1038/s41573-019-0012-9. View

17.

Nikolic J, Belot L, Raux H, Legrand P, Gaudin Y, Albertini A . Structural basis for the recognition of LDL-receptor family members by VSV glycoprotein. Nat Commun. 2018; 9(1):1029. PMC: 5847621. DOI: 10.1038/s41467-018-03432-4. View

18.

Srivastava A . In vivo tissue-tropism of adeno-associated viral vectors. Curr Opin Virol. 2016; 21:75-80. PMC: 5138125. DOI: 10.1016/j.coviro.2016.08.003. View

19.

Zhong L, Li B, Mah C, Govindasamy L, Agbandje-Mckenna M, Cooper M . Next generation of adeno-associated virus 2 vectors: point mutations in tyrosines lead to high-efficiency transduction at lower doses. Proc Natl Acad Sci U S A. 2008; 105(22):7827-32. PMC: 2402387. DOI: 10.1073/pnas.0802866105. View

20.

Woodham A, Skeate J, Sanna A, Taylor J, Da Silva D, Cannon P . Human Immunodeficiency Virus Immune Cell Receptors, Coreceptors, and Cofactors: Implications for Prevention and Treatment. AIDS Patient Care STDS. 2016; 30(7):291-306. PMC: 4948215. DOI: 10.1089/apc.2016.0100. View