Apolipoprotein E (
ApoE) is a multifunctional
protein critical for lipid metabolism and
cholesterol homeostasis. In addition to being a well known genetic determinant of both neurodegenerative and
cardiovascular diseases,
ApoE is frequently involved in various
viral infection-related diseases.
Human ApoE protein is functionally polymorphic with three
isoforms, namely,
ApoE2,
ApoE3, and
ApoE4, with markedly altered
protein structures and functions.
ApoE4 is associated with increased susceptibility to
infection with herpes simplex virus type-1 and HIV. Conversely,
ApoE4 protects against hepatitis C virus and
hepatitis B virus infection. With the outbreak of
coronavirus disease 2019,
ApoE4 has been shown to determine the incidence and progression of
severe acute respiratory syndrome coronavirus 2 infection. These findings clearly indicate the critical role of
ApoE in
viral infection. Furthermore,
ApoE polymorphism has various or even opposite effects in these
infection processes, which are partly related to the structural features that distinguish the different
ApoE statuses. In the current review, we summarize the emerging relationship between
ApoE and
viral infection, discuss the potential mechanisms, and identify future directions that may help to advance our understanding of the link between
ApoE and
viral infection.