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10.1128/JVI.02321-08

http://scihub22266oqcxt.onion/10.1128/JVI.02321-08
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C2668499!2668499!19211764
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suck abstract from ncbi


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pmid19211764      J+Virol 2009 ; 83 (9): 4297-307
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  • Protein X of Borna Disease Virus Inhibits Apoptosis and Promotes Viral Persistence in the Central Nervous Systems of Newborn-Infected Rats ? #MMPMID19211764
  • Poenisch M; Burger N; Staeheli P; Bauer G; Schneider U
  • J Virol 2009[May]; 83 (9): 4297-307 PMID19211764show ga
  • Borna disease virus (BDV) is a neurotropic member of the order Mononegavirales with noncytolytic replication and obligatory persistence in cultured cells and animals. Here we show that the accessory protein X of BDV represents the first mitochondrion-localized protein of an RNA virus that inhibits rather than promotes apoptosis induction. Rat C6 astroglioma cells persistently infected with wild-type BDV were significantly more resistant to death receptor-dependent and -independent apoptotic stimuli than uninfected cells or cells infected with a BDV mutant expressing reduced amounts of X. Confocal microscopy demonstrated that X colocalizes with mitochondria and expression of X from plasmid DNA rendered human 293T and mouse L929 cells resistant to apoptosis induction. A recombinant virus encoding a mutant X protein unable to associate with mitochondria (BDV-XA6A7) failed to block apoptosis in C6 cells. Furthermore, Lewis rats neonatally infected with BDV-XA6A7 developed severe neurological symptoms and died around day 30 postinfection, whereas all animals infected with wild-type BDV remained healthy and became persistently infected. TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) staining revealed a significant increase in the number of apoptotic cells in the brain of BDV-XA6A7-infected animals, whereas the numbers of CD3+ T lymphocytes were comparable to those detected in animals infected with wild-type BDV. Our data thus indicate that inhibition of apoptosis by X promotes noncytolytic viral persistence and is required for the survival of cells in the central nervous system of BDV-infected animals.
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