SV40 T-Antigen Amino Acid Changes that Disrupt Cul-7 or Bub-1 Binding Do Not Globally Distort the T-Common Region.

Background: Amino acids 1-107 of the SV40 T antigen constitute a functionally important and complex region. Cellular proteins, Hsc70, Bub-1, Cul-7, and Rb, each of which is involved in cell growth control or genomic stability, bind within this portion of the T antigen. Mutational analysis has mapped the J domain/Hsc70, Bub-1, and the Rb binding motifs.

CD8+ T cells targeting a single immunodominant epitope are sufficient for elimination of established SV40 T antigen-induced brain tumors.

Immunotherapy of established solid tumors is rarely achieved, and the mechanisms leading to success remain to be elucidated. We previously showed that extended control of advanced-stage autochthonous brain tumors is achieved following adoptive transfer of naive C57BL/6 splenocytes into sublethally irradiated line SV11 mice expressing the SV40 T Ag (T Ag) oncoprotein, and was associated with in vivo priming of CD8(+) T cells (T(CD8)) specific for the dominant epitope IV (T Ag residues 404-411). Using donor lymphocytes derived from mice that are tolerant to epitope IV or a newly characterized transgenic mouse line expressing an epitope IV-specific TCR, we show that epitope IV-specific T(CD8) are a necessary component of the donor pool and that purified naive epitope IV-specific T(CD8) are sufficient to promote complete and rapid regression of established tumors.

JC virus T'135, T'136 and T'165 proteins interact with cellular p107 and p130 in vivo and influence viral transformation potential.

The JC virus (JCV) regulatory proteins, large T antigen, small t antigen, T'135, T'136, and T'165, are encoded by five transcripts alternatively spliced from the viral early precursor mRNA. T antigen and the T' proteins share N-terminal amino acid sequences that include the L x CxE and J domains, motifs in SV40 T antigen known to mediate binding to the retinoblastoma (Rb) proteins and Hsc70, respectively. In this study, G418-resistant cell lines were created that express wild-type or mutant JCV T antigen and T' proteins individually or in combination.

The chloromethylketone protease inhibitor AAPF(CMK) also targets ATP-dependent helicases and SAP-domain proteins.

We have been studying a nuclear protease, which appears to be involved in cellular transformation, as well as in infections with high-risk human papillomaviruses (HPVs). This protease has a chymotrypsin-like substrate specificity and the chloromethylketone inhibitor AAPF(CMK) is a potent (and relatively selective) inhibitor of it. Recently, we have observed that AAPF(CMK) has potent effects in some model systems which appear not to be mediated by decreases in the nuclear protease.

A structural rationale for SV40 Vp1 temperature-sensitive mutants and their complementation.

Two groups of temperature-sensitive (ts) mutants, termed ts B and ts C, have mutations in the major capsid protein of SV40, Vp1. These mutants have virion assembly defects at the nonpermissive temperature, but can complement one another when two mutants, one from each group, coinfect a cell. A third group of mutants, termed ts BC, have related phenotypes, but do not complement other mutants.