Herpes simplex type 1 activates glycolysis through engagement of the enzyme 6-phosphofructo-1-kinase (PFK-1)

被引:84
作者
Abrantes, Juliana L. [1 ,2 ]
Alves, Cristiane M. [1 ]
Costa, Jessica [1 ]
Almeida, Fabio C. L. [3 ]
Sola-Penna, Mauro [4 ]
Fontes, Carlos Frederico L. [2 ]
Souza, Thiago Moreno L. [1 ]
机构
[1] Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Lab Referencia Influenza & Viroses Exantematicas, Lab Virus Resp & Sarampo, Rio De Janeiro, RJ, Brazil
[2] Univ Fed Rio de Janeiro, Inst Bioquim Med, Lab Estrutura & Regulacao Prot & ATPase, Programa Posgrad Quim Biol, Rio De Janeiro, RJ, Brazil
[3] Univ Fed Rio de Janeiro, Inst Bioquim Med, Ctr Nacl Ressonancia Magnet Nucl Jiri Jonas, Rio De Janeiro, RJ, Brazil
[4] Univ Fed Rio de Janeiro, Dept Farmacos, Fac Farm, Lab Enzimol & Controle Metab, Rio De Janeiro, RJ, Brazil
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2012年 / 1822卷 / 08期
关键词
HSV-1; PFK-1; Glycolysis; SKELETAL-MUSCLE; 6-PHOSPHOFRUCTO-1-KINASE; IMMUNODEFICIENCY-VIRUS TYPE-1; BREAST-CANCER CELLS; GLUCOSE-METABOLISM; DIFFERENTIAL EXPRESSION; PROTEIN-SYNTHESIS; VERO CELLS; PHOSPHOFRUCTOKINASE; INFECTION; PHOSPHORYLATION;
D O I
10.1016/j.bbadis.2012.04.011
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Viruses such as HIV, HCV, Mayaro and HCMV affect cellular metabolic pathways, including glycolysis. Although some studies have suggested that the inhibition of glycolysis affects HSV-1 replication and that HSV-1-infected eyes have increased lactate production, the mechanisms by which HSV-1 induces glycolysis have never been investigated in detail. In this study, we observed an increase in glucose uptake, lactate efflux and ATP content in HSV-1-infected cells. HSV-1 triggered a MOI-dependent increase in the activity of phosphofructokinase-1 (PFK-1), a key rate-limiting enzyme of the glycolytic pathway. After HSV-1 infection, we observed increased PFK-1 expression, which increased PFK-1 total activity, and the phosphorylation of this enzyme at serine residues. HSV-1-induced glycolysis was associated with increased ATP content, and these events were critical for viral replication. In summary, our results suggest that HSV-1 triggers glycolysis through a different mechanism than other herpesviruses, such as HCMV. Thus, this study contributes to a better understanding of HSV-1 pathogenesis and provides insights into novel targets for antiviral therapy. (C) 2012 Elsevier B.V. All rights reserved.
引用
收藏
页码:1198 / 1206
页数:9
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