title: Viral load and its relationship to quinolinic acid, TNF alpha, and IL-6 levels in the CNS of retroviral infected mice.
abstract: Mouse models of infection of the central nervous system (CNS) have been used to study retroviral-induced neurologic disease. Ecotropic-neurotropic murine leukemia virus (MuLV) infection of susceptible neonatal mice causes a neurologic disease characterized by progressive hindlimb paralysis. The lesions consist of chronic noninflammatory spongiform change predominantly involving brainstem and spinal cord. Two molecularly cloned strains of MuLV, ts-1, a temperature-sensitive mutant of Moloney MuLV, and pNE-8, derived from a feral mouse isolate Cas-Br-E, were used in this study. Infected mice were sacrificed at regular intervals postinoculation throughout the time-course of disease. The neuropathology was evaluated using standard histological and immunohistopathological techniques. Tissue concentrations of viral proteins and potentially cytotoxic factors were compared with the histopathology in select regions of the CNS. Areas of extensive vacuolation with neuronal and oligodendroglial infection were observed in spinal cord, brainstem, and cerebellum. High titers of infectious virus were observed within CNS lesions, whereas low titers were observed in morphologically uninvolved areas. Western blot analysis revealed abundant production of viral envelope proteins, which correlated well with infectious virus titers. Serum quinolinic acid (QUIN) concentrations in both groups of noninfected and infected mice were similar. However, CNS tissue concentrations of QUIN, TNF alpha, and IL-6 in ts-1 infected mice were significantly higher than in pNE-8 infected or noninfected mice. The difference in concentration of these factors may be the result of greater activation of macrophages/microglia in ts-1 infected mice. During murine retroviral encephalitis, CNS damage may be mediated by direct infection of CNS cells and may be enhanced by indirect effects of neurotoxic factors possibly secreted by infected/activated macrophages.
authors.affiliation: Brain Research Institute, University of California Los Angeles.
authors.forename: R M
authors.initials: RM
authors.lastname: Nagra
authors.forename: M P
authors.initials: MP
authors.lastname: Heyes
authors.forename: C A
authors.initials: CA
authors.lastname: Wiley
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D001933:Brain Stem / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism*; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000302:isolation & purification; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008979:Moloney murine leukemia virus / Q000235:genetics; D009154:Mutation; D009422:Nervous System Diseases / Q000473:pathology / Q000821:virology*; D011247:Pregnancy; D017378:Quinolinic Acid / Q000378:metabolism*; D012192:Retroviridae Infections / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014412:Tumor Virus Infections / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D014759:Viral Envelope Proteins; D017378:Quinolinic Acid