title: Herpes simplex type 1 activates glycolysis through engagement of the enzyme 6-phosphofructo-1-kinase (PFK-1).
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.
  
  
  CONCLUSIONS
  ►HSV-1 activates glycolysis by PFK-1 activation. ►In HSV-1-infected cells PFK-1 synthesis is up-regulated and phosphorylated at serine residues. ►PFK-1 knockdown impairs HSV-1 replication. ►HSV-1-mediated glycolysis activation increases ATP content.
authors.affiliation: Laboratório de Estrutura e Regulação de Proteínas e ATPases, Programa de Pós-Graduação em Química Biológica, Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, RJ, Brazil. abrantes@bioqmed.ufrj.br
authors.forename: Juliana L
authors.initials: JL
authors.lastname: Abrantes
authors.forename: Cristiane M
authors.initials: CM
authors.lastname: Alves
authors.forename: Jessica
authors.initials: J
authors.lastname: Costa
authors.forename: Fabio C L
authors.initials: FC
authors.lastname: Almeida
authors.forename: Mauro
authors.initials: M
authors.lastname: Sola-Penna
authors.forename: Carlos Frederico L
authors.initials: CF
authors.lastname: Fontes
authors.forename: Thiago Moreno L
authors.initials: TM
authors.lastname: Souza
mesh_terms: D000818:Animals; D002470:Cell Survival; D002522:Chlorocebus aethiops; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D006561:Herpes Simplex / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D010732:Phosphofructokinase-1 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D014709:Vero Cells
chemical_list: D010732:Phosphofructokinase-1; D005947:Glucose