Document Detail


Both viral transcription and replication are reduced when the rabies virus nucleoprotein is not phosphorylated.
MedLine Citation:
PMID:  11932380     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Rabies virus nucleoprotein (N) plays vital roles in regulation of viral RNA transcription and replication by encapsidation of the nascent genomic RNA. Rabies virus N is phosphorylated, and previous studies demonstrated that mutation of the phosphorylated serine at position 389 to alanine resulted in reduction of viral transcription and/or replication of a rabies virus minigenome. In the present study, we mutated the serine (S) at position 389 to alanine (A), glycine (G), aspartic acid (D), asparagine (N), glutamic acid (E), and glutamine (Q) and examined the effects of these mutations on rabies virus transcription and replication in the minigenome. Furthermore, mutations from S to A, S to D, and S to E were also incorporated into the full-length infectious virus. Mutation of the serine to each of the other amino acids resulted in the synthesis of an unphosphorylated N and reduction of viral transcription and replication in the minigenome. Mutations from S to A and S to D also resulted in reduction of both viral transcription and replication in full-length infectious viruses. Growth curve studies indicated that production of the mutant virus with the S-to-A mutation (L16A) was as much as 10,000-fold less than that of the wild-type virus (L16). Northern blot hybridization with rabies virus gene probes revealed that the rates of viral transcription and replication were reduced by as much as 10-fold in the mutant viruses when the N was not phosphorylated. Interpretation of the data from the minigenome system and the full-length infectious virus indicates that phosphorylation of rabies virus N is necessary for replication. Further studies involving cycloheximide treatment of infected cells revealed that viral transcription was also reduced when the N was not phosphorylated. Taken together, these results provide definitive evidence that N phosphorylation plays an important role in the processes of rabies virus transcription and replication.
Authors:
Xianfu Wu; Xiaoming Gong; Heather D Foley; Matthias J Schnell; Zhen F Fu
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of virology     Volume:  76     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  2002 May 
Date Detail:
Created Date:  2002-04-04     Completed Date:  2002-05-10     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4153-61     Citation Subset:  IM    
Affiliation:
Department of Pathology, The University of Georgia, Athens, Georgia 30602, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Mutagenesis, Site-Directed
Nucleocapsid / genetics,  metabolism*
Nucleocapsid Proteins
Phosphorylation
Plasmids
RNA, Viral / metabolism
Rabies virus / genetics,  growth & development*,  metabolism*
Transcription, Genetic*
Transfection
Virus Replication*
Grant Support
ID/Acronym/Agency:
AI-51560/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Nucleocapsid Proteins; 0/RNA, Viral; 0/nucleocapsid protein, Rabies virus
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