Author:
Wongtrakul Jeerang,Thongtan Thananya,Pannengpetch Supitcha,Wikan Nitwara,Kantamala Doungnapa,Kumrapich Benjawan,Suwan Warissara,Smith Duncan R.
Abstract
AbstractDengue virus (DENV) is an arthropod-borne Flavivirus that can cause a range of symptomatic disease in humans. There are four dengue viruses (DENV 1 to 4) and infection with one DENV only provides transient protection against a heterotypic virus. Second infections are often more severe as the disease is potentiated by antibodies from the first infection through a process known as antibody dependent enhancement (ADE) of infection. Phosphorylation is a major post-translational modification that can have marked effects on a number of processes. To date there has been little information on the phosphorylation changes induced by DENV infection. This study aimed to determine global phosphoproteome changes induced by DENV 2 in U937 cells infected under an ADE protocol. A 2-dimensional electrophoretic approach coupled with a phosphoprotein-specific dye and mass spectroscopic analysis identified 15 statistically significant differentially phosphorylated proteins upon DENV 2 infection. One protein identified as significantly differentially phosphorylated, pyruvate kinase M2 (PKM2) was validated. Treatment with a PKM2 inhibitor modestly reduced levels of infection and viral output, but no change was seen in cellular viral protein levels, suggesting that PKM2 acts on exocytic virus release. While the effect of inhibition of PKM2 was relatively modest, the results highlight the need for a greater understanding of the role of phosphoproteins in DENV infection.
Funder
National Research Council of Thailand
Publisher
Springer Science and Business Media LLC
Reference54 articles.
1. Back, A. T. & Lundkvist, A. Dengue viruses—an overview. Infect. Ecol. Epidemiol. 3, 1–21 (2013).
2. Brady, O. J. et al. Refining the global spatial limits of dengue virus transmission by evidence-based consensus. PLoS Negl. Trop. Dis. 6, 1–15 (2012).
3. Murray, N. E. A., Quam, M. B. & Wilder-Smith, A. Epidemiology of dengue: Past, present and future prospects. Clin. Epidemiol. 5, 299–309 (2013).
4. Kalayanarooj, S. & Nimmannitya, S. Clinical and laboratory presentations of dengue patients with different serotypes. Dengue Bull. 24, 53–59 (2000).
5. Anantapreecha, S. et al. Serological and virological features of dengue fever and dengue haemorrhagic fever in Thailand from 1999 to 2002. Epidemiol. Infect. 133, 503–507 (2005).
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献