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  • 标题:Amphotropic murine leukemia viruses induce spongiform encephalomyelopathy
  • 本地全文:下载
  • 作者:Carsten Münk ; Jürgen Löhler ; Vladimir Prassolov
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:1997
  • 卷号:94
  • 期号:11
  • 页码:5837-5842
  • DOI:10.1073/pnas.94.11.5837
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Recombinants of amphotropic murine leukemia virus (A-MuLV) have found widespread use in retroviral vector systems due to their ability to efficiently and stably infect cells of several different species, including human. Previous work has shown that replication-competent recombinants containing the amphotropic env gene, encoding the major SU envelope glycoprotein that determines host tropism, induce lymphomas in vivo. We show here that these viruses also induce a spongiform encephalomyelopathy in mice inoculated perinatally. This fatal central nervous system disease is characterized by noninflammatory spongiform lesions of nerve and glial cells and their processes, and is associated with moderate astro- and microgliosis. The first clinical symptoms are ataxia, tremor, and spasticity, progressing to complete tetraparesis and incontinence, and finally death of the animal. Sequences within the amphotropic env gene are necessary for disease induction. Coinfection of A-MuLV recombinants with nonneuropathogenic ecotropic or polytropic MuLV drastically increases the incidence, degree, and distribution of the neurodegenerative disorder. The consequence of these results in view of the use of A-MuLV recombinants in the clinic is discussed.
  • 关键词:gene therapy ; retrovirus ; retrovirus pathogenicity ; central nervous system ; packaging cell lines
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