title: Dengue virus type 2 (DENV2)-induced oxidative responses in monocytes from glucose-6-phosphate dehydrogenase (G6PD)-deficient and G6PD normal subjects.
abstract: BACKGROUND
  Dengue virus is endemic in peninsular Malaysia. The clinical manifestations vary depending on the incubation period of the virus as well as the immunity of the patients. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is prevalent in Malaysia where the incidence is 3.2%. It has been noted that some G6PD-deficient individuals suffer from more severe clinical presentation of dengue infection. In this study, we aim to investigate the oxidative responses of DENV2-infected monocytes from G6PD-deficient individuals.
  
  
  METHODS
  Monocytes from G6PD-deficient individuals were infected with DENV2 and infection rate, levels of oxidative species, nitric oxide (NO), superoxide anions (O2-), and oxidative stress were determined and compared with normal controls.
  
  
  RESULTS
  Monocytes from G6PD-deficient individuals exhibited significantly higher infection rates compared to normal controls. In an effort to explain the reason for this enhanced susceptibility, we investigated the production of NO and O2- in the monocytes of individuals with G6PD deficiency compared with normal controls. We found that levels of NO and O2- were significantly lower in the DENV-infected monocytes from G6PD-deficient individuals compared with normal controls. Furthermore, the overall oxidative stress in DENV-infected monocytes from G6PD-deficient individuals was significantly higher when compared to normal controls. Correlation studies between DENV-infected cells and oxidative state of monocytes further confirmed these findings.
  
  
  CONCLUSIONS
  Altered redox state of DENV-infected monocytes from G6PD-deficient individuals appears to augment viral replication in these cells. DENV-infected G6PD-deficient individuals may contain higher viral titers, which may be significant in enhanced virus transmission. Furthermore, granulocyte dysfunction and higher viral loads in G6PD-deificient individuals may result in severe form of dengue infection.
authors.affiliation: Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Penang, Malaysia.
authors.forename: Abdullah Ahmed
authors.initials: AA
authors.lastname: Al-Alimi
authors.affiliation: Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Penang, Malaysia.
authors.forename: Syed A
authors.initials: SA
authors.lastname: Ali
authors.affiliation: Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Penang, Malaysia.
authors.forename: Faisal Muti
authors.initials: FM
authors.lastname: Al-Hassan
authors.affiliation: Department of Microbiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.
authors.forename: Fauziah Mohd
authors.initials: FM
authors.lastname: Idris
authors.affiliation: Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Penang, Malaysia.
authors.forename: Sin-Yeang
authors.initials: SY
authors.lastname: Teow
authors.affiliation: Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Penang, Malaysia.
authors.forename: Narazah
authors.initials: N
authors.lastname: Mohd Yusoff
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003716:Dengue Virus / Q000187:drug effects / Q000276:immunology* / Q000502:physiology*; D005955:Glucosephosphate Dehydrogenase Deficiency; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D008296:Malaysia; D008297:Male; D009000:Monocytes / Q000276:immunology* / Q000821:virology*; D009569:Nitric Oxide / Q000032:analysis; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000032:analysis; D013481:Superoxides / Q000032:analysis; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
chemical_list: D017382:Reactive Oxygen Species; D013481:Superoxides; D009569:Nitric Oxide