Mayaro virus infection alters glucose metabolism in cultured cells through activation of the enzyme 6-phosphofructo 1-kinase

Departamento de Bioquímica Medica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Molecular and Cellular Biochemistry (Impact Factor: 2.39). 12/2004; 266(1-2):191-8. DOI: 10.1023/B:MCBI.0000049154.17866.00
Source: PubMed


Although it is well established that cellular transformation with tumor virus leads to changes on glucose metabolism, the effects of cell infection by non-transforming virus are far to be completely elucidated. In this study, we report the first evidence that cultured Vero cells infected with the alphavirus Mayaro show several alterations on glucose metabolism. Infected cells presented a two fold increase on glucose consumption, accompanied by an increment in lactate production. This increase in glycolytic flux was also demonstrated by a significant increase on the activity of 6-phosphofructo 1-kinase, one of the regulatory enzymes of glycolysis. Analysis of the kinetic parameters revealed that the regulation of 6-phosphofructo 1-kinase is altered in infected cells, presenting an increase in V
max along with a decrease in K
m for fructose-6-phosphate. Another fact contributing to an increase in enzyme activity was the decrease in ATP levels observed in infected cells. Additionally, the levels of fructose 2,6-bisphosphate, a potent activator of this enzyme, was significantly reduced in infected cells. These observations suggest that the increase in PFK activity may be a compensatory cellular response to the viral-induced metabolic alterations that could lead to an impairment of the glycolytic flux and energy production. (Mol Cell Biochem 266: 191–198, 2004)

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Available from: Mauro Sola-Penna, May 04, 2014
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    • "Viruses rely on the metabolic network of their cellular hosts to provide energy and building blocks for viral replication (Coroadinha et al., 2006; El-Bacha et al., 2004; Munger et al., 2006, 2008). In this study, a total of 7 differential proteins related to energy metabolism including glycolysis (enolase), tricarboxylic acid cycle (aconitase, isocitrate dehydrogenase and malic enzyme) and oxidative phosphorylation (ATP synthase, ATPase and NADH dehydrogenase) were indentified in salivary gland, midgut and C6/36 cells by 2D DIGE combining MS after DENV-2 infection (Fig. 1, Tables 1–3). "
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    ABSTRACT: The interaction between dengue virus (DENV) and vector mosquitoes are still poorly understood at present. In this study, 2-D DIGE combined with MS was used to analyze the differential proteomes of Aedes albopictus salivary gland, midgut and C6/36 cells induced by DENV-2. Our results indicated that the virus infection regulated several functional classes of proteins. Among them, 26 were successfully analyzed by real-time RT-PCR. The mRNA levels of 15 were the highest in salivary gland, 2 in midgut and none in C6/36 cells, however, 18 were the least in fat body compared to other organs. Interestingly, the changes of differential proteins mRNA were the most obvious in fat body post-infection. Chaperone, cytoskeleton and energy metabolism enzyme were the most down- or up- regulated proteins after DENV-2 infection. The abundant expression of these proteins in salivary gland may relate to its high susceptibility.
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    • "It has been shown that an increase in the uptake and utilization of glucose are events observed during the infection of mammalian cells with alpha, rhabdo, herpes, ortomyxo and retroviruses [2], [3], [4], [5], [6], [7]. The increased utilization of glucose by infected cells supplies both ATP and biosynthetic precursors required for virus replication, as observed in Mayaro and Sindbis viruses infections [2], [3], [4]. However, this may represent an anti-viral cellular response, as in the case of Human Immunodeficiency Virus (HIV) infection [8]. "
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    ABSTRACT: The metabolic resources crucial for viral replication are provided by the host. Details of the mechanisms by which viruses interact with host metabolism, altering and recruiting high free-energy molecules for their own replication, remain unknown. Sindbis virus, the prototype of and most widespread alphavirus, causes outbreaks of arthritis in humans and serves as a model for the study of the pathogenesis of neurological diseases induced by alphaviruses in mice. In this work, respirometric analysis was used to evaluate the effects of Sindbis virus infection on mitochondrial bioenergetics of a mouse neuroblastoma cell lineage, Neuro 2a. The modulation of mitochondrial functions affected cellular ATP content and this was synchronous with Sindbis virus replication cycle and cell death. At 15 h, irrespective of effects on cell viability, viral replication induced a decrease in oxygen consumption uncoupled to ATP synthesis and a 36% decrease in maximum uncoupled respiration, which led to an increase of 30% in the fraction of oxygen consumption used for ATP synthesis. Decreased proton leak associated to complex I respiration contributed to the apparent improvement of mitochondrial function. Cellular ATP content was not affected by infection. After 24 h, mitochondria dysfunction was clearly observed as maximum uncoupled respiration reduced 65%, along with a decrease in the fraction of oxygen consumption used for ATP synthesis. Suppressed respiration driven by complexes I- and II-related substrates seemed to play a role in mitochondrial dysfunction. Despite the increase in glucose uptake and glycolytic flux, these changes were followed by a 30% decrease in ATP content and neuronal death. Taken together, mitochondrial bioenergetics is modulated during Sindbis virus infection in such a way as to favor ATP synthesis required to support active viral replication. These early changes in metabolism of Neuro 2a cells may form the molecular basis of neuronal dysfunction and Sindbis virus-induced encephalitis.
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    • "Another interesting result of our study is that five enzymes involved in the glycolysis pathway were up-regulated. Increased glucose uptake and glycolytic enzyme activity due to viral infection have been found in other studies [39,40]. The induction of glycolytic proteins involved in energy production is also found in CHIKV and DENV-2 infections [9]. "
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