Apolipoprotein E genotype and hepatitis C, HIV and herpes simplex disease risk: a literature review

ApoE4 seems to be protective against chronic hepatitis C virus infection and retards fibrosis progression. In contrast apoE4 enhances the fusion rate of human immunodeficiency virus with target cell membranes, resulting in accelerated cell entry and faster disease progression. Its association with human immunodeficiency virus-associated dementia remains controversial. Regarding herpes simplex virus infection, apoE4 intensifies virus latency and is associated with increased oxidative damage of the central nervous system, and there is some evidence that herpes simplex virus infection in combination with the apoE4 genotype may be associated with an increased risk of Alzheimer's disease. In addition to reviewing available data from human trials, evidence derived from a variety of cell culture and animal models are considered in this review in order to provide mechanistic insights into observed association between apoE4 genotype and viral disease infection and pathology.Viral diseases are a global health problem. Like many other diseases, differences in the pathological features and outcome of viral diseases exist, which are undoubtedly in part due to genetic variations in the host. Apolipoprotein E (apoE), in addition to being a central mediator of lipoprotein metabolism, has an ever increasing 'repertoire' of biological functions [1,2]. As will be reviewed here, accumulating evidence indicates that apoE genotype could be an important host genetic factor affecting infectious disease risk.The mature apoE protein results from the proteolytic cleavage of a 317-amino acid precursor protein and contains 299 amino acids with a molecular weight of approximately 34 kDa [3]. ApoE is synthesised primarily by the liver. It is estimated that 20-40% of total apoE is produced by extrahepatic tissues with the brain glial cells and macrophages expressing relatively high amounts, with lesser amounts produced by the kidneys, adrenals, spleen, testis and the skin [4-7]. In the circulation