PMID- 11829347 OWN - NLM STAT- MEDLINE DCOM- 20020226 LR - 20190513 IS - 0022-3069 (Print) IS - 0022-3069 (Linking) VI - 61 IP - 1 DP - 2002 Jan TI - Accumulation of beta-amyloid precursor protein in axons correlates with CNS expression of SIV gp41. PG - 85-90 AB - 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. FAU - Mankowski, J L AU - Mankowski JL AD - Division of Comparative Medicine, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. FAU - Queen, S E AU - Queen SE FAU - Tarwater, P M AU - Tarwater PM FAU - Fox, K J AU - Fox KJ FAU - Perry, V H AU - Perry VH LA - eng GR - RR000116/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - J Neuropathol Exp Neurol JT - Journal of neuropathology and experimental neurology JID - 2985192R RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Membrane Glycoproteins) RN - 0 (Retroviridae Proteins) RN - 0 (SIV envelope protein gp41) RN - 0 (Viral Envelope Proteins) SB - IM MH - Amyloid beta-Protein Precursor/*metabolism MH - Animals MH - Axons/*metabolism/pathology MH - Brain/*metabolism/pathology/*virology MH - Disease Models, Animal MH - Encephalitis, Viral/*metabolism/pathology/virology MH - Humans MH - Immunohistochemistry MH - Macaca nemestrina MH - Membrane Glycoproteins/genetics/*metabolism MH - Retroviridae Proteins/genetics/*metabolism MH - Simian Acquired Immunodeficiency Syndrome/*metabolism/pathology/virology MH - Simian Immunodeficiency Virus/genetics/*physiology MH - Viral Envelope Proteins/genetics/metabolism MH - Viral Load MH - Virus Replication EDAT- 2002/02/07 10:00 MHDA- 2002/02/28 10:01 CRDT- 2002/02/07 10:00 PHST- 2002/02/07 10:00 [pubmed] PHST- 2002/02/28 10:01 [medline] PHST- 2002/02/07 10:00 [entrez] AID - 10.1093/jnen/61.1.85 [doi] PST - ppublish SO - J Neuropathol Exp Neurol. 2002 Jan;61(1):85-90. doi: 10.1093/jnen/61.1.85.