Document Detail

Effects of Tat proteins and Tat mutants of different human immunodeficiency virus type 1 clades on glial JC virus early and late gene transcription.
MedLine Citation:
PMID:  23152365     Owner:  NLM     Status:  MEDLINE    
Polyomavirus JC (JCV) is the aetiological agent of progressive multifocal leukoencephalopathy (PML), a frequently fatal infection of the brain afflicting nearly 4% of AIDS patients in the USA. Human immunodeficiency virus type 1 (HIV-1) Tat, acting together with cellular proteins at the JCV non-coding control region (NCCR), can stimulate JCV DNA transcription and replication. Tat in the brain is secreted by HIV-1-infected cells and incorporated by oligodendroglia, cells capable of infection by JCV. Thus far the effects of Tat on JCV have been studied primarily with protein encoded by the HIV-1 B clade most common in North America. Here, we determine the abilities of Tat from different HIV-1 clades to alter JCV early and late gene transcription and DNA replication initiated at the JCV origin. Tat from all clades tested stimulates both JCV early and late gene promoters, with clade B Tat being significantly most effective. Tat proteins from the HIV-1 clades display parallel patterns of differences in their effects on HIV-1 and JCV transcription, suggesting that Tat effects in both cases are mediated by the same cellular proteins. Clade B Tat is most effective at directing Smad mediators of tumour growth factor beta and cellular partner Purα to the NCCR. Tat proteins from all non-B clades inhibit initiation of JCV DNA replication. The effectiveness of HIV-1 clade B Tat at promoting JCV transcriptional and replicative processes highlights a need for further investigation to determine which molecular aspects of Tat from distinct HIV-1 substrains can contribute to the course of PML development in neuroAIDS.
Clayton A Wright; Jonas A Nance; Edward M Johnson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-11-14
Journal Detail:
Title:  The Journal of general virology     Volume:  94     ISSN:  1465-2099     ISO Abbreviation:  J. Gen. Virol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-19     Completed Date:  2013-04-17     Revised Date:  2014-03-07    
Medline Journal Info:
Nlm Unique ID:  0077340     Medline TA:  J Gen Virol     Country:  England    
Other Details:
Languages:  eng     Pagination:  514-23     Citation Subset:  IM    
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MeSH Terms
Amino Acid Sequence
Cell Line
DNA, Viral / genetics
DNA-Binding Proteins / genetics,  metabolism
Gene Expression Regulation, Viral / drug effects*
Gene Products, tat / genetics,  metabolism*
HIV-1 / classification*,  genetics*
JC Virus / drug effects*
Molecular Sequence Data
Neuroglia / virology*
Smad4 Protein / genetics,  metabolism
Transcription Factors / genetics,  metabolism
Virus Replication
Grant Support
Reg. No./Substance:
0/DNA, Viral; 0/DNA-Binding Proteins; 0/Gene Products, tat; 0/PURA protein, human; 0/SMAD4 protein, human; 0/Smad4 Protein; 0/Transcription Factors

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