Retrovirus-induced spongiform neurodegeneration is mediated by unique central nervous system viral targeting and expression of env alone.

Retrovirus-induced spongiform neurodegeneration is mediated by unique central nervous system viral targeting and expression of env alone.

Li Ying; Cardona Sandra M; Traister Russell S; Lynch William P

Journal of virology

2011

2011-03

Certain murine leukemia viruses (MLVs) can induce progressive noninflammatory spongiform neurodegeneration similar to that caused by prions. The primary MLV determinants responsible have been mapped to within the env gene; however, it has remained unclear how env mediates disease, whether non-Env viral components are required, and what central nervous system (CNS) cells constitute the critical CNS targets. To address these questions, we examined the effect of transplanting engraftable C17.2 neural stem cells engineered to pseudotype, disseminate, and trans-complement neurovirulent (CasBrE, CasE, and CasES) or non-neurovirulent (Friend and SFF-FE) env sequences (SU or SU/TM) within the CNS using either the "non-neurovirulent" amphotropic helper virus, 4070A, or pgag-polgpt (a nonpackaged vector encoding Gag-Pol). These studies revealed that acute

Animals; Cell Line; Friend murine leukemia virus/genetics/metabolism; Humans; Leukemia Virus; Mice; Murine/genetics/*metabolism/pathogenicity; Nerve Degeneration; Neural Stem Cells/pathology/virology; Neurodegenerative Diseases/pathology/*virology; Retroviridae Infections/pathology/*virology; Viral Envelope Proteins/genetics/*metabolism; Virulence

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