[Neurotoxicity of human foamy virus in transgenic mice].
Human foamy virus (HFV) is a human retrovirus originally isolated from patients with various neoplastic and degenerative diseases. Similarly to other human retroviruses, HFV encodes the three structural retroviral genes, gag, pol and env, and an additional region containing three open reading frames, bel-1 to bel-3. Bel-1 activates transcription of the long terminal repeat of HFV and also of HIV. Until today it has not been possible to identify HFV as the causative agent of any disease. In order to identify a possible pathogenic potential of HFV, we have introduced parts of the HFV genome into the germ line of mice. Our studies with transgenic mice have shown that HFV transgenes encompassing the bel region are transiently transcribed between midgestation and birth at moderate levels in various tissues. Expression is then suppressed, but resumes after a latency of several weeks in a restricted range of tissues and accumulate extensively in single cells. This is associated with a progressive degenerative disease of the central nervous system and of striated muscle. These findings provide the first evidence of a disease induced by HFV and suggest that HFV might also act as a human pathogen in neurological diseases. Moreover, the transgenic mouse model will be useful for studying the molecular basis of HFV-induced neurotoxicity, the role of individual disease-associated HFV genes, and the regulation of retroviral latency.
Aguzzi
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Institut für Neuropathologie, Departement Pathologie, Zürich, Schweiz.
D000818:Animals; D001921:Brain / Q000473:pathology / Q000821:virology*; D001932:Brain Neoplasms / Q000821:virology*; D015870:Gene Expression; D015752:Genes, env; D015750:Genes, gag; D015751:Genes, pol; D006678:HIV / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009135:Muscular Diseases / Q000821:virology*; D009422:Nervous System Diseases / Q000821:virology*; D016366:Open Reading Frames; D012091:Repetitive Sequences, Nucleic Acid; D016092:Spumavirus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics
D014764:Viral Proteins