title: Temporal central and peripheral nervous system changes induced by a paralytogenic mutant of Moloney murine leukemia virus TB.
abstract: BACKGROUND
  The temporal localization of cellular targets for viral replication and the morphopathogenesis of neurodegeneration in the central nervous system (CNS) and peripheral nervous system induced by ts1, a neuropathogenic and lymphocytopathic mutant of Moloney murine leukemia virus-TB, were studied in the highly susceptible FVB/N mouse strain in order to better understand the mechanisms of this neurodegenerative disease.
  
  
  METHODS
  Newborn FVB/N mice were inoculated intraperitoneally with 0.1 ml of viral suspension containing 10(6) to 10(7) infectious units/ml. The mice were observed daily for clinical signs of disease and killed at specific time points. Their nervous system tissues were collected and processed for light and electron microscopy and for immunohistochemical viral-antigen detection.
  
  
  RESULTS
  ts1-Infected FVB/N mice developed a rapidly progressive wasting disease that culminated in hindleg paralysis or paraplegia 30 to 35 days postinoculation (pi).
  
  
  CONCLUSIONS
  Clear evidence of CNS lesions involving the cerebellar ventricular system, the grey and white matter of the brain stem and the spinal cord were seen as early as 5 to 10 days pi. These lesions, which began as mild perivascular and paraventricular neuropil spongiform changes and cytoplasmic vacuolation of neuronal and glial cell processes, progressed in severity with time and culminated in almost complete destruction of the white and gray matter in the brain stem and the cervical and lumbar spinal cord. Viruses were detected as early as 5 to 10 days pi in the fourth ventricle choroid plexus and ventricular lumen and budding from endothelial cells within the brain stem and cerebellum. Endothelial, ependymal, microglial, astroglial, and oligodendroglial cells were positive for gp70env. Astroglial and microglial cell proliferation with microglial syncytia formation was detected only within the areas showing spongiform degeneration. Viral replication was consistently high in the capillary endothelial cells of those areas showing spongiform degeneration, whereas in the glial cells, relatively few budding viruses were present. Neurodegeneration was accompanied by demyelinization within the CNS and peripheral nervous system and by hindleg muscle degeneration and necrosis. Multiple cellular targets for ts1 viral infection and replication were detected within the nervous system. The presence of budding virus and the immunodetection of viral antigen in the choroid plexus and ependymal cells of the fourth ventricle and the central canal of the spinal cord demonstrated that cerebrospinal fluid as well as blood can disseminate virus within the CNS. Pathologic and functional changes within the blood-brain barrier and glial system probably account for the neuronal necrosis and spongiform changes that result in paralysis induced by ts1 infection.
authors.affiliation: Texas A & M University, Department of Veterinary Pathobiology, College of Veterinary Medicine, College Station.
authors.forename: G
authors.initials: G
authors.lastname: Stoica
authors.forename: O
authors.initials: O
authors.lastname: Illanes
authors.forename: S I
authors.initials: SI
authors.lastname: Tasca
authors.forename: P K
authors.initials: PK
authors.lastname: Wong
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology; D001933:Brain Stem / Q000473:pathology; D002490:Central Nervous System / Q000382:microbiology / Q000473:pathology*; D004805:Ependyma / Q000473:pathology; D008526:Medulla Oblongata / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D008979:Moloney murine leukemia virus / Q000472:pathogenicity*; D009422:Nervous System Diseases / Q000382:microbiology / Q000473:pathology*; D010243:Paralysis / Q000382:microbiology* / Q000473:pathology; D017933:Peripheral Nervous System / Q000382:microbiology / Q000473:pathology*; D012584:Sciatic Nerve / Q000473:pathology; D013116:Spinal Cord / Q000382:microbiology / Q000473:pathology; D013997:Time Factors; D014779:Virus Replication