Selective virus resistance conferred by expression of Borna disease virus nucleocapsid components.
Persistent viral infections can render host cells resistant to superinfection with closely related viruses by largely uncharacterized mechanisms. We present evidence for superinfection exclusion in brains of Borna disease virus (BDV)-infected rats and in persistently infected Vero cells, and we suggest that acquired resistance to BDV is due to unbalanced intracellular levels of viral nucleocapsid components. We observed that expression of BDV protein P, N, or X rendered human cells resistant to subsequent challenge with BDV but not with other RNA viruses, indicating that incorrect stoichiometry of nucleocapsid components selectively blocked the polymerase activity of incoming viruses. Vero cells containing high levels of an untranslatable BDV-N transcript remained virus susceptible, demonstrating that viral protein rather than RNA mediated resistance. Transient overexpression of BDV-P in persistently infected Vero cells was also remarkably effective against BDV, indicating that the intracellular balance of viral nucleocapsid components could serve as a target for future therapeutic antiviral strategies.
Geib
Till
T
Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, Germany.
Sauder
Christian
C
Venturelli
Sascha
S
Hässler
Christel
C
Staeheli
Peter
P
Schwemmle
Martin
M
D000818:Animals; D000831:Animals, Newborn; D001890:Borna Disease / Q000473:pathology / Q000821:virology; D001891:Borna disease virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D002460:Cell Line; D002522:Chlorocebus aethiops; D015870:Gene Expression; D005814:Genes, Viral; D006801:Humans; D019590:Nucleocapsid Proteins / Q000235:genetics / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015163:Superinfection / Q000517:prevention & control; D014162:Transfection; D014709:Vero Cells; D014762:Viral Interference / Q000235:genetics / Q000502:physiology*; D014774:Virulence
D019590:Nucleocapsid Proteins; D011994:Recombinant Proteins