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.
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.
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.
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.
An estimated 50 to 100 million cases of dengue fever occur each year worldwide. Among these, there are 200,000 to 500,000 cases of life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Factors contributing to the development of DHF/DSS are not yet fully identified. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is prevalent in Southeast Asian countries where dengue is also endemic. Besides affecting normal function of erythrocytes, G6PD deficiency also affects other cells by causing abnormal cellular redox. Altered redox state of cells may render them less effective in clearing up microbial and viral infections. Here we confirm previous findings that monocytes from G6PD-deficinet individuals support better dengue virus replication. In addition, we show that reduced production of reactive oxygen, and nitrogen species and elevated levels of oxidative stress are responsible for the enhanced viral replication. We suggest that redox imbalance observed in infected monocytes from G6PD-deficient individuals may facilitate dengue transmission and affect clinical outcome. However, a handful of studies carried out in areas where both G6PD deficiency and dengue are endemic, reveal no statistically significant correlation between severity of Dengue and G6PD deficiency. Well-designed studies are needed to demonstrate that G6PD-deficient individuals are at risk of severe dengue.