RT Journal Article
T1 Guanosine inhibits hepatitis C virus replication and increases indel frequencies, associated with altered intracellular nucleotide pools.
A1 Sabariegos, Rosario
A1 Ortega-Prieto, Ana María
A1 Diaz-Martínez, Luis
A1 Grande-Pérez, Ana
A1 García Crespo, Carlos
A1 Gallego, Isabel
A1 De Ávila, Ana Isabel
A1 Albentosa-González, Laura
A1 Soria, María Eugenia
A1 Gastaminza, Pablo
A1 Domingo, Esteban
A1 Perales, Celia
A1 Mas, Antonio
K1 Virología
K1 Virus de la hepatitis
K1 Nucleósidos
K1 Nucleótidos
K1 Genómica
K1 Acido ribonucleico - Síntesis
K1 ARN - Síntesis
AB 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.
PB PLOS
YR 2022
FD 2022-01-27
LK https://hdl.handle.net/10630/38179
UL https://hdl.handle.net/10630/38179
LA eng
NO 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
NO The team at CBMSO belongs to the Global Virus Network (GVN). Plan Propio from Universidad de Castilla-La Mancha and Universidad de Malaga are acknowledged. Institutional grantsfrom the Fundacio´n Ramo´n Areces and Banco Santander to the CBMSO are also acknowledged. Brenda Martı´nez-Gonza´lez and Lucı´a Va´zquez-Sirvent are acknowledge for their adviceon the statistics of S2 Fig. Piet de Groot is acknowledged for the critical reading of themanuscript.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 19 ene 2026