2026-05-30T02:32:55Zhttps://riuma.uma.es/rest/oai/requestoai:riuma.uma.es:10630/381792026-02-03T11:32:13Zcom_10630_2254col_10630_37953
RIUMA. Repositorio Institucional de la Universidad de Málaga
author
Sabariegos, Rosario
author
Ortega-Prieto, Ana María
author
Diaz-Martínez, Luis
author
Grande-Pérez, Ana
author
García Crespo, Carlos
author
Gallego, Isabel
author
De Ávila, Ana Isabel
author
Albentosa-González, Laura
author
Soria, María Eugenia
author
Gastaminza, Pablo
author
Domingo, Esteban
author
Perales, Celia
author
Mas, Antonio
2025-03-20T11:51:25Z
2025-03-20T11:51:25Z
2022-01-27
Sabariegos R, Ortega-Prieto AM, Díaz-Martínez L, Grande-Pérez A, García Crespo C, Gallego I, et al. (2022) Guanosine inhibits hepatitis C virus replication and increases indel frequencies, associated with altered intracellular nucleotide pools. PLoS Pathog 18(1): e1010210. https://doi.org/10.1371/journal.ppat.1010210
https://hdl.handle.net/10630/38179
10.1371/journal.ppat.1010210
In the course of experiments aimed at deciphering the inhibition mechanism of mycophenolic acid and ribavirin in hepatitis C virus (HCV) infection, we observed an inhibitory effect of the nucleoside guanosine (Gua). Here, we report that Gua, and not the other standard nucleosides, inhibits HCV replication in human hepatoma cells. Gua did not directly inhibit the in vitro polymerase activity of NS5B, but it modified the intracellular levels of nucleoside di- and tri-phosphates (NDPs and NTPs), leading to deficient HCV RNA replication and reduction of infectious progeny virus production. Changes in the concentrations of NTPs or NDPs modified NS5B RNA polymerase activity in vitro, in particular de novo RNA synthesis and template switching. Furthermore, the Gua-mediated changes were associated with a significant increase in the number of indels in viral RNA, which may account for the reduction of the specific infectivity of the viral progeny, suggesting the presence of defective genomes. Thus, a proper NTP:NDP balance appears to be critical to ensure HCV polymerase fidelity and minimal production of defective genomes.
eng
Attribution 4.0 Internacional
Virología
Virus de la hepatitis
Nucleósidos
Nucleótidos
Genómica
Acido ribonucleico - Síntesis
ARN - Síntesis
Guanosine inhibits hepatitis C virus replication and increases indel frequencies, associated with altered intracellular nucleotide pools.
journal article
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Plos pathogens Ana.pdf