title: Cellular tropism and localization in the rodent nervous system of a neuropathogenic variant of Friend murine leukemia virus.
abstract: BACKGROUND
  We studied PVC-211 murine leukemia virus (MuLV) (1), a neuropathogenic variant of Friend MuLV, to determine its cellular tropism and distribution in the nervous system of infected rats and the factors that affected disease expression.
  
  
  METHODS
  Rats from five different strains and mice from 3 strains were inoculated intracerebrally or intraperitoneally from birth to 10 days of age and observed for signs of neurologic disease and tumors for 24 weeks. Nervous system pathology, MuLV gp70 expression, and virus production were evaluated weekly for 4 weeks after perinatal infection of Fisher (F344) rats. Blood-brain-barrier integrity and ultrastructure were evaluated in 21-day-old symptomatic infected rats. Microvessel and mixed glial cell cultures were prepared from brains of infected and uninfected 21-day-old F344 rats and evaluated for virus production, MuLV gp70 expression, and the presence of PVC-211 MuLV DNA.
  
  
  RESULTS
  Tremor, ataxia, spasticity, and hindlimb weakness occurred in rats and mice as early as 3 weeks after neonatal infection. Severity, latency, and progression varied among mouse and rat strains but exposure to PVC-211 MuLV before 6 days of age was required for disease expression. Rapid PVC-211 MuLV replication in brain capillary endothelial cells (BCEC) early in the perinatal period was followed by widespread astrogliosis, neuropil vacuolation, and finally, neuronal degeneration in the spinal cord, brainstem, cerebellum, and subcortex. MuLV gp70 expression in vivo increased during infection, was restricted to BCEC, but was not associated with perivascular inflammatory infiltrates. BCEC cultured from microvessel preparations but not astrocytes or microglia in mixed glial cell cultures isolated from infected rats contained PVC-211 MuLV DNA, expressed MuLV gp70, and produced infectious virus.
  
  
  CONCLUSIONS
  The rapid replication of PVC-211 MuLV that occurs in the nervous system of infected rodents is restricted to BCEC. These infected BCEC appear to play a critical role in initiating the astroglial response in this neurodegenerative process through mechanisms that remain to be defined.
authors.affiliation: Retrovirus Research Center, Department of Veterans Affairs Medical Center, Baltimore, Maryland.
authors.forename: P M
authors.initials: PM
authors.lastname: Hoffman
authors.forename: E F
authors.initials: EF
authors.lastname: Cimino
authors.forename: D S
authors.initials: DS
authors.lastname: Robbins
authors.forename: R D
authors.initials: RD
authors.lastname: Broadwell
authors.forename: J M
authors.initials: JM
authors.lastname: Powers
authors.forename: S K
authors.initials: SK
authors.lastname: Ruscetti
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D005622:Friend murine leukemia virus / Q000235:genetics / Q000302:isolation & purification*; D014644:Genetic Variation / Q000235:genetics; D007942:Leukemia, Experimental / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009420:Nervous System / Q000382:microbiology* / Q000473:pathology* / Q000648:ultrastructure; D009457:Neuroglia / Q000382:microbiology / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D017207:Rats, Sprague-Dawley; D014779:Virus Replication
chemical_list: D004279:DNA, Viral