title: Viral persistence in neurons alters synaptic plasticity and cognitive functions without destruction of brain cells.
abstract: Neurons have a restricted expression of MHC heavy chain molecules which prevents presentation of antigens of infecting viruses. As a result, such infected cells escape immune surveillance and allow the establishment of noncytolytic persistent infection. Here we show that a chronic noncytolytic viral infection both in vitro and in vivo selectively perturbed the expression of GAP-43, a protein that plays a central role in neuronal plasticity processes accompanying learning and memory. GAP-43 expression was greatly decreased in the hippocampus, an area of heightened viral replication, while synaptic density was preserved. Concurrently, the ability to learn tasks was significantly impaired in these persistently infected mice. Yet, infected neurons remained free from structural injury.
authors.affiliation: Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA. Juanct@Scripps.edu
authors.forename: J C
authors.initials: JC
authors.lastname: de la Torre
authors.forename: M
authors.initials: M
authors.lastname: Mallory
authors.forename: M
authors.initials: M
authors.lastname: Brot
authors.forename: L
authors.initials: L
authors.lastname: Gold
authors.forename: G
authors.initials: G
authors.lastname: Koob
authors.forename: M B
authors.initials: MB
authors.lastname: Oldstone
authors.forename: E
authors.initials: E
authors.lastname: Masliah
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology* / Q000821:virology; D005260:Female; D019922:GAP-43 Protein; D008216:Lymphocytic Choriomeningitis / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000502:physiology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009473:Neuronal Plasticity; D009474:Neurons / Q000821:virology*; D016716:PC12 Cells; D012367:RNA, Viral; D051381:Rats; D017735:Virus Latency
chemical_list: D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D012367:RNA, Viral