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

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Abstract

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. Highlights: [U+25BA]HSV-1 activates glycolysis by PFK-1 activation. [U+25BA]In HSV-1-infected cells PFK-1 synthesis is up-regulated and phosphorylated at serine residues. [U+25BA]PFK-1 knockdown impairs HSV-1 replication. [U+25BA]HSV-1-mediated glycolysis activation increases ATP content. © 2012 Elsevier B.V.

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Abrantes, J. L., Alves, C. M., Costa, J., Almeida, F. C. L., Sola-Penna, M., Fontes, C. F. L., & Souza, T. M. L. (2012). Herpes simplex type 1 activates glycolysis through engagement of the enzyme 6-phosphofructo-1-kinase (PFK-1). Biochimica et Biophysica Acta - Molecular Basis of Disease, 1822(8), 1198–1206. https://doi.org/10.1016/j.bbadis.2012.04.011

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