Possible retroviral origin of prion disease: could prion disease be reconsidered as a preleukemia syndrome?
A retroviral etiology might explain why amyloid plaque and/or spongiosis are or are not associated with neuronal death in prion diseases. While retroviral genes themselves may be responsible for neuronal death, a retrovirus may also cause mutations in cellular genes. Hence, the prion gene may be altered by a retrovirus in the same way as a cellular proto-oncogene is altered to produce an oncogene, either by transduction or by integration of the provirus in its vicinity. In both cases, the resulting abnormal prion protein, acting as a catalyst, may induce the formation of amyloid plaques. In addition, a wild type retrovirus may recombine to the vesicular stomatitis virus (VSV) to give rise to a pseudotyped retrovirus able to induce spongiosis. It is reported here that in scrapie, a blood monocytoid cell proliferates in vitro. If confirmed in other species, this raises the question of the potential link between prion disease and leukemia. Indeed neurovirulent strains of murine leukemia virus, a slow acting retrovirus, are known to induce spongiform encephalopathies. A preliminary attempt to purify reverse transcriptase by chromatography, using the classical protocol, failed because of the presence of a prion-like protein secreted by the blood mononuclear cells which stuck to the phosphocellulose column. Therefore, if a retrovirus is present in prion diseases, it would be evidenced only in animals developing the disease in the absence of prion protein. From this point of view, mice obtained in 1997 by the group of D. Dormont in France, offer a unique opportunity to test the retroviral hypothesis.
Labat
M L
ML
Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort, France.
D000818:Animals; D006801:Humans; D011289:Preleukemia / Q000209:etiology / Q000821:virology*; D017096:Prion Diseases / Q000209:etiology / Q000635:transmission / Q000821:virology*; D000090063:Proto-Oncogene Mas; D012190:Retroviridae; D012192:Retroviridae Infections / Q000821:virology*