title: Accumulation of beta-amyloid precursor protein in axons correlates with CNS expression of SIV gp41.
abstract: Axonal damage represented by accumulation of beta-amyloid precursor protein (beta-APP) develops in numerous central nervous system (CNS) diseases including human immunodeficiency virus (HIV) infection. To study the underlying mechanisms of axonal damage associated with HIV CNS infection, the amount of axonal beta-APP immunostaining in the corpus callosum of 24 simian immunodeficiency virus (SIV)-infected macaques and 3 control macaques was measured by computerized image analysis. The amounts of beta-APP accumulation were then compared with time post-inoculation, extent and character of CNS inflammation, and viral load in the CNS measured by the amount of immunohistochemical staining for the viral transmembrane protein gp41. Significant increases over control values were present in 10 of 24 SIV-infected animals. SIV encephalitis was present in 9 of the 10 animals with elevated beta-APP Increases in beta-APP correlated most strongly with levels of SIV gp41 in the brain (p = 0.005), but significant associations with macrophage infiltration and microglial activation (p = 0.04) and infiltration by cytotoxic lymphocytes (p = 0.05) also were identified. These data demonstrate that beta-APP accumulation in the white matter of SIV-infected macaques develops during SIV infection in close correlation with levels of viral replication and may serve as a sensitive marker of neuronal/axonal damage mediated by viral proteins.
authors.affiliation: Division of Comparative Medicine, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Mankowski
authors.forename: S E
authors.initials: SE
authors.lastname: Queen
authors.forename: P M
authors.initials: PM
authors.lastname: Tarwater
authors.forename: K J
authors.initials: KJ
authors.lastname: Fox
authors.forename: V H
authors.initials: VH
authors.lastname: Perry
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D004195:Disease Models, Animal; D018792:Encephalitis, Viral / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D008254:Macaca nemestrina; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D012191:Retroviridae Proteins / Q000235:genetics / Q000378:metabolism*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D019562:Viral Load; D014779:Virus Replication
chemical_list: D016564:Amyloid beta-Protein Precursor; D008562:Membrane Glycoproteins; D012191:Retroviridae Proteins; C082614:SIV envelope protein gp41; D014759:Viral Envelope Proteins