2-Deoxy-D-glucose inhibits lymphocytic choriomeningitis virus
propagation by targeting glycoprotein N-glycosylation

J 2023

2-Deoxy-D-glucose inhibits lymphocytic choriomeningitis virus propagation by targeting glycoprotein N-glycosylation

BAĎUROVÁ, Lucia, Katarína POLČICOVÁ, Božena OMASTA, Ingrid OVEČKOVÁ, Eva KOCIANOVÁ et. al.

Základní údaje

Originální název

2-Deoxy-D-glucose inhibits lymphocytic choriomeningitis virus propagation by targeting glycoprotein N-glycosylation

Autoři

BAĎUROVÁ, Lucia, Katarína POLČICOVÁ, Božena OMASTA, Ingrid OVEČKOVÁ, Eva KOCIANOVÁ a Jana TOMÁŠKOVÁ

Vydání

Virology Journal, LONDON, BMC, 2023, 1743-422X

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10607 Virology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.800 v roce 2022

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1186/s12985-023-02082-3

UT WoS

001000224200002

Klíčová slova anglicky

Arenavirus; LCMV; Cell metabolism; Glycolysis; 2-Deoxy-D-glucose; Glycoprotein; N-linked glycosylation; Virus-host interaction; Antiviral therapy

Štítky

RIV ne

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 2. 4. 2024 11:37, Mgr. Eva Dubská

Anotace

V originále

Background Increased glucose uptake and utilization via aerobic glycolysis are among the most prominent hallmarks of tumor cell metabolism. Accumulating evidence suggests that similar metabolic changes are also triggered in many virus-infected cells. Viral propagation, like highly proliferative tumor cells, increases the demand for energy and macromolecular synthesis, leading to high bioenergetic and biosynthetic requirements. Although significant progress has been made in understanding the metabolic changes induced by viruses, the interaction between host cell metabolism and arenavirus infection remains unclear. Our study sheds light on these processes during lymphocytic choriomeningitis virus (LCMV) infection, a model representative of the Arenaviridae family.Methods The impact of LCMV on glucose metabolism in MRC-5 cells was studied using reverse transcription-quantitative PCR and biochemical assays. A focus-forming assay and western blot analysis were used to determine the effects of glucose deficiency and glycolysis inhibition on the production of infectious LCMV particles.Results Despite changes in the expression of glucose transporters and glycolytic enzymes, LCMV infection did not result in increased glucose uptake or lactate excretion. Accordingly, depriving LCMV-infected cells of extracellular glucose or inhibiting lactate production had no impact on viral propagation. However, treatment with the commonly used glycolytic inhibitor 2-deoxy-D-glucose (2-DG) profoundly reduced the production of infectious LCMV particles. This effect of 2-DG was further shown to be the result of suppressed N-linked glycosylation of the viral glycoprotein.Conclusions Although our results showed that the LCMV life cycle is not dependent on glucose supply or utilization, they did confirm the importance of N-glycosylation of LCMV GP-C. 2-DG potently reduces LCMV propagation not by disrupting glycolytic flux but by inhibiting N-linked protein glycosylation. These findings highlight the potential for developing new, targeted antiviral therapies that could be relevant to a wider range of arenaviruses.

Citovat

BAĎUROVÁ, Lucia, Katarína POLČICOVÁ, Božena OMASTA, Ingrid OVEČKOVÁ, Eva KOCIANOVÁ a Jana TOMÁŠKOVÁ. 2-Deoxy-D-glucose inhibits lymphocytic choriomeningitis virus propagation by targeting glycoprotein N-glycosylation. Virology Journal. LONDON: BMC, 2023, roč. 20, č. 1, s. 1-18. ISSN 1743-422X. Dostupné z: https://dx.doi.org/10.1186/s12985-023-02082-3.

@article{2361457,
   author = {Baďurová, Lucia and Polčicová, Katarína and Omasta, Božena and Ovečková, Ingrid and Kocianová, Eva and Tomášková, Jana},
   article_location = {LONDON},
   article_number = {1},
   doi = {http://dx.doi.org/10.1186/s12985-023-02082-3},
   keywords = {Arenavirus; LCMV; Cell metabolism; Glycolysis; 2-Deoxy-D-glucose; Glycoprotein; N-linked glycosylation; Virus-host interaction; Antiviral therapy},
   language = {eng},
   issn = {1743-422X},
   journal = {Virology Journal},
   title = {2-Deoxy-D-glucose inhibits lymphocytic choriomeningitis virus propagation by targeting glycoprotein N-glycosylation},
   url = {https://doi.org/10.1186/s12985-023-02082-3},
   volume = {20},
   year = {2023}
}

TY  - JOUR
ID  - 2361457
AU  - Baďurová, Lucia - Polčicová, Katarína - Omasta, Božena - Ovečková, Ingrid - Kocianová, Eva - Tomášková, Jana
PY  - 2023
TI  - 2-Deoxy-D-glucose inhibits lymphocytic choriomeningitis virus propagation by targeting glycoprotein N-glycosylation
JF  - Virology Journal
VL  - 20
IS  - 1
SP  - 1-18
EP  - 1-18
PB  - BMC
SN  - 1743422X
KW  - Arenavirus
KW  - LCMV
KW  - Cell metabolism
KW  - Glycolysis
KW  - 2-Deoxy-D-glucose
KW  - Glycoprotein
KW  - N-linked glycosylation
KW  - Virus-host interaction
KW  - Antiviral therapy
UR  - https://doi.org/10.1186/s12985-023-02082-3
N2  - Background Increased glucose uptake and utilization via aerobic glycolysis are among the most prominent hallmarks of tumor cell metabolism. Accumulating evidence suggests that similar metabolic changes are also triggered in many virus-infected cells. Viral propagation, like highly proliferative tumor cells, increases the demand for energy and macromolecular synthesis, leading to high bioenergetic and biosynthetic requirements. Although significant progress has been made in understanding the metabolic changes induced by viruses, the interaction between host cell metabolism and arenavirus infection remains unclear. Our study sheds light on these processes during lymphocytic choriomeningitis virus (LCMV) infection, a model representative of the Arenaviridae family.Methods The impact of LCMV on glucose metabolism in MRC-5 cells was studied using reverse transcription-quantitative PCR and biochemical assays. A focus-forming assay and western blot analysis were used to determine the effects of glucose deficiency and glycolysis inhibition on the production of infectious LCMV particles.Results Despite changes in the expression of glucose transporters and glycolytic enzymes, LCMV infection did not result in increased glucose uptake or lactate excretion. Accordingly, depriving LCMV-infected cells of extracellular glucose or inhibiting lactate production had no impact on viral propagation. However, treatment with the commonly used glycolytic inhibitor 2-deoxy-D-glucose (2-DG) profoundly reduced the production of infectious LCMV particles. This effect of 2-DG was further shown to be the result of suppressed N-linked glycosylation of the viral glycoprotein.Conclusions Although our results showed that the LCMV life cycle is not dependent on glucose supply or utilization, they did confirm the importance of N-glycosylation of LCMV GP-C. 2-DG potently reduces LCMV propagation not by disrupting glycolytic flux but by inhibiting N-linked protein glycosylation. These findings highlight the potential for developing new, targeted antiviral therapies that could be relevant to a wider range of arenaviruses.
ER  -

BAĎUROVÁ, Lucia, Katarína POLČICOVÁ, Božena OMASTA, Ingrid OVEČKOVÁ, Eva KOCIANOVÁ a Jana TOMÁŠKOVÁ. 2-Deoxy-D-glucose inhibits lymphocytic choriomeningitis virus propagation by targeting glycoprotein N-glycosylation. \textit{Virology Journal}. LONDON: BMC, 2023, roč.~20, č.~1, s.~1-18. ISSN~1743-422X. Dostupné z: https://dx.doi.org/10.1186/s12985-023-02082-3.

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