Directed Molecular Evolution of an Engineered Gammaretroviral Envelope Protein with Dual Receptor Use Shows Stable Maintenance of Both Receptor Specificities
| Autor: | Shervin Bahrami, Jonas Thomsen, Rodrigo Alvear-Perez, Finn Skou Pedersen, Xavier Iturrioz, Catherine Llorens-Cortes, Kristina Pagh Friis |
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| Přispěvatelé: | Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropeptides centraux et régulations hydrique et cardiovasculaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre interdisciplinaire de recherche en biologie (CIRB), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre interdisciplinaire de recherche en biologie (CIRB), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Labex MemoLife, Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
[SDV]Life Sciences [q-bio] viruses Immunology B-cell receptor Microbiology Genomic Instability Cell Line Receptors G-Protein-Coupled Viral vector 03 medical and health sciences Viral Envelope Proteins Viral envelope Viral entry Virology Murine leukemia virus Animals Humans [CHIM]Chemical Sciences Receptor ComputingMilieux_MISCELLANEOUS Apelin receptor Gammaretrovirus Apelin Receptors biology Virus Internalization biology.organism_classification Molecular biology Virus-Cell Interactions Viral Tropism 030104 developmental biology Insect Science Receptors Virus Directed Molecular Evolution Xenotropic and Polytropic Retrovirus Receptor |
| Zdroj: | Friis, K P, Iturrioz, X, Thomsen, J, Alvear-Perez, R, Bahrami, S, Llorens-Cortes, C & Pedersen, F S 2015, ' Directed Molecular Evolution of an Engineered Gammaretroviral Envelope Protein with Dual Receptor Use Shows Stable Maintenance of Both Receptor Specificities ', Journal of Virology, vol. 90, no. 3, pp. 1647-56 . https://doi.org/10.1128/JVI.02013-15 Journal of Virology Journal of Virology, American Society for Microbiology, 2016, 90 (3), pp.1647-1656. ⟨10.1128/JVI.02013-15⟩ Journal of Virology, 2016, 90 (3), pp.1647-1656. ⟨10.1128/JVI.02013-15⟩ |
| ISSN: | 1098-5514 0022-538X |
| Popis: | We have previously reported the construction of a murine leukemia virus-based replication-competent gammaretrovirus (SL3-AP) capable of utilizing the human G protein-coupled receptor APJ (hAPJ) as its entry receptor and its natural receptor, the murine Xpr1 receptor, with equal affinities. The apelin receptor has previously been shown to function as a coreceptor for HIV-1, and thus, adaptation of the viral vector to this receptor is of significant interest. Here, we report the molecular evolution of the SL3-AP envelope protein when the virus is cultured in cells harboring either the Xpr1 or the hAPJ receptor. Interestingly, the dual receptor affinity is maintained even after 10 passages in these cells. At the same time, the chimeric viral envelope protein evolves in a distinct pattern in the apelin cassette when passaged on D17 cells expressing hAPJ in three separate molecular evolution studies. This pattern reflects selection for reduced ligand-receptor interaction and is compatible with a model in which SL3-AP has evolved not to activate hAPJ receptor internalization. IMPORTANCE Few successful examples of engineered retargeting of a retroviral vector exist. The engineered SL3-AP envelope is capable of utilizing either the murine Xpr1 or the human APJ receptor for entry. In addition, SL3-AP is the first example of an engineered retrovirus retaining its dual tropism after several rounds of passaging on cells expressing only one of its receptors. We demonstrate that the virus evolves toward reduced ligand-receptor affinity, which sheds new light on virus adaptation. We provide indirect evidence that such reduced affinity leads to reduced receptor internalization and propose a novel model in which too rapid receptor internalization may decrease virus entry. |
| Databáze: | OpenAIRE |
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