Münk C, Löhler J, Prassolov V, Just U, Stockschläder M, Stocking C
Department of Cell and Virus Genetics, Heinrich-Pette-Institut für experimentelle Virologie und Immunologie, Martinistrasse 52, D-20251 Hamburg, Germany.
Proc Natl Acad Sci U S A. 1997 May 27;94(11):5837-42. doi: 10.1073/pnas.94.11.5837.
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.
嗜双性小鼠白血病病毒（A-MuLV）重组体因其能够高效稳定地感染包括人类在内的几种不同物种的细胞，已在逆转录病毒载体系统中得到广泛应用。先前的研究表明，含有嗜双性env基因的具有复制能力的重组体，该基因编码决定宿主嗜性的主要SU包膜糖蛋白，在体内可诱发淋巴瘤。我们在此表明，这些病毒在围产期接种的小鼠中还会诱发海绵状脑脊髓病。这种致命的中枢神经系统疾病的特征是神经细胞和神经胶质细胞及其突起出现非炎性海绵状病变，并伴有中度星形胶质细胞增生和小胶质细胞增生。最初的临床症状是共济失调、震颤和痉挛，进而发展为完全性四肢瘫痪和大小便失禁，最终动物死亡。嗜双性env基因内的序列是疾病诱导所必需的。A-MuLV重组体与非神经致病性亲嗜性或多嗜性MuLV共同感染会显著增加神经退行性疾病的发病率、程度和分布。讨论了这些结果对于临床使用A-MuLV重组体的影响。
