Altered DNA binding and replication activities of JC Virus T-antigen mutants

John E. Tavis, Richard J. Frisque

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Ten mutations were introduced into the JC virus (JCV) T antigen within a region corresponding to the SV40 T-antigen DNA binding domain (SV40 amino acids 131 to 220); nine of these increased homology between the two proteins in sequences critical for SV40 T antigen DNA binding. All mutant JCV T antigens bound to JCV and SV40 origins of DNA replication. Binding efficiency relative to that of wild-type JCV T antigen ranged from 83 to 301 % for the JCV binding sites and from 44 to 240% for the SV40 binding sites. Nine mutant proteins promoted viral DNA replication in primary human fetal glial (PHFG) and CV-1 cells. In PHFG cells, promotion of DNA replication ranged from 26 to 220% relative to that of wild-type T antigen; in CV-1 cells it ranged from 14 to 522%. Coding sequences for five mutant proteins were transferred into the hybrid virus M1(SV40) [M1(SV40) contains coding sequences from JCV and regulatory sequences from SV40]. Wild-type T antigen promoted replication weakly from the SV40 origin in these hybrid viruses in CV-1 cells (2% that from the JCV origin); replication driven by the mutant proteins ranged from 110 to 412% of that induced by the wild-type protein. Efficient specific DNA binding by a mutant T antigen was not a reliable indicator of that mutant protein's ability to promote DNA replication.

Original languageEnglish (US)
Pages (from-to)239-250
Number of pages12
JournalVirology
Volume183
Issue number1
DOIs
StatePublished - Jul 1991

All Science Journal Classification (ASJC) codes

  • Virology

Fingerprint Dive into the research topics of 'Altered DNA binding and replication activities of JC Virus T-antigen mutants'. Together they form a unique fingerprint.

Cite this