title: ApoE4 is more efficient than E3 in brain access by herpes simplex virus type 1.
abstract: Apolipoprotein E (ApoE) plays a relevant role in herpes simplex type 1 (HSV-1) infection of the CNS; after infection by the hematogenous route, the viral neuroinvasiveness directly depends on the APOE gene dose. To analyze the effect of ApoE isoforms on the HSV-1 infectivity to the brain, we have used a model of hematogenous infection of mice humanized for the ApoE3 or the ApoE4 alleles, and we have analyzed the presence of viral DNA in several organs by real time quantitative PCR. We have found that animals expressing human ApoE4 present very high levels of virus in the brain when compared to those expressing the ApoE3 allele; in contrast, there were no significant differences in the viral levels found in peripheral organs. Apolipoprotein E4 seems to facilitate the entry and/or spread of HSV-1 in the brain much more efficiently than E3, pointing to a novel potential mechanism underlying the susceptibility to neurodegenerative processes associated with the ApoE4 allele.
authors.affiliation: Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Javier S
authors.initials: JS
authors.lastname: Burgos
authors.forename: Carlos
authors.initials: C
authors.lastname: Ramirez
authors.forename: Isabel
authors.initials: I
authors.lastname: Sastre
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Bullido
authors.forename: Fernando
authors.initials: F
authors.lastname: Valdivieso
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism / Q000821:virology; D000818:Animals; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000378:metabolism*; D001769:Blood / Q000378:metabolism / Q000821:virology; D001923:Brain Chemistry; D005260:Female; D006561:Herpes Simplex / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D007239:Infections; D051379:Mice; D013131:Spine / Q000378:metabolism / Q000821:virology
chemical_list: D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E