in people with chronic diseases such as diabetes and asthma. Polymorphisms (normal variations) in particular genes have been linked with an increased risk of severe dengue complications. Examples include the genes coding for the proteins TNFα, mannan-binding lectin, CTLA4, TGFβ, DC-SIGN, PLCE1, and particular forms of human leukocyte antigen from gene variations of HLA-B. A common genetic abnormality, especially in Africans, known as glucose-6-phosphate dehydrogenase deficiency, appears to increase the risk. Polymorphisms in the genes for the vitamin D receptor and FcγR seem to offer protection against severe disease in secondary dengue infection. Mechanism When a mosquito carrying dengue virus bites a person, the virus enters the skin together with the mosquito's saliva. It binds to and enters white blood cells, and reproduces inside the cells while they move throughout the body. The white blood cells respond by producing several signaling proteins, such as cytokines and interferons, which are responsible for many of the symptoms, such as the fever, the flu-like symptoms, and the severe pains. In severe infection, the virus production inside the body is greatly increased, and many more organs (such as the liver and the bone marrow) can be affected. Fluid from the bloodstream leaks through the wall of small blood vessels into body cavities due to capillary permeability. As a result, less blood circulates in the blood vessels, and the blood pressure becomes so low that it cannot supply sufficient blood to vital organs. Furthermore, dysfunction of the bone marrow due to infection of the stromal cells leads to reduced numbers of platelets, which are necessary for effective blood clotting; this increases the risk of bleeding, the other major complication of dengue fever. Viral replication Once inside the skin, dengue virus binds to Langerhans cells (a population of dendritic cells in the skin that identifies pathogens). The virus enters the cells through binding between viral proteins and membrane proteins on the Langerhans cell, specifically, the C-type lectins called DC-SIGN, mannose receptor and CLEC5A. DC-SIGN, a non-specific receptor for foreign material on dendritic cells, seems to be the main point of entry. The dendritic cell moves to the nearest lymph node. Meanwhile, the virus genome is translated in membrane-bound vesicles on the cell's endoplasmic reticulum, where the cell's protein synthesis apparatus produces new viral proteins that replicate the viral RNA and begin to form viral particles. Immature virus particles are transported to the Golgi apparatus, the part