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

Abstract

Apolipoprotein E is a polymorphic and multifunctional protein with numerous roles in lipoprotein metabolism. The three common isoforms apoE2, apoE3 and apoE4 show isoform-specific functional properties including different susceptibilities to diseases. ApoE4 is an accepted risk factor for Alzheimer's disease and cardiovascular disorders. Recently, associations between apoE4 and infectious diseases have been demonstrated. This review summarises how apoE4 may be involved in the infection incidence and associated pathologies of specific infectious diseases, namely hepatitis C, human immunodeficiency virus disease and herpes simplex.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.

Figure 1

Potential mechanisms of the impact of apoE4 on viral treatment response, fibrosis progression in recurrent HCV infection as well as protection against HCV associated severe liver damage. LDL: low density lipoprotein, LDL-R: low density lipoprotein receptor, HCV: hepatitis C virus

Figure 2

Potential mechanisms for apoE4 mediated faster progression of HIV disease. LDL: low density lipoprotein, LDL-R: low density lipoprotein receptor, HIV: human immunodeficiency virus, HSPG: heparin sulphate proteoglycans.

Figure 3

Possible mechanisms of the impact of apoE4 on increased neurodegeneration and HIV-associated dementia. Tat: transactivator protein, LRP: low density lipoprotein receptor-related protein, HIV: human immunodeficiency virus.

Figure 4

Possible mechanisms of the adverse effects of apoE4 on the outcome of herpes labialis and the increased HSV-induced oxidative damage in the CNS that possibly increases the susceptibility to AD. HSV: herpes simplex virus, HSPG: heparin sulphate proteoglycans, LDL: low density lipoprotein, iNOS: inducible nitric oxide synthase, NO: nitric oxide, CNS: central nervous system, AD: Alzheimer's disease.