Inhibition of human papillomavirus-16 long control region activity by interferon-gamma overcome by p300 overexpression

Although interferons (IFNs) are currently used in the treatment of various human papillomavirus (HPV)-associated lesions, their mechanisms of action are still unclear. In this study, we clearly demonstrated that IFN-gamma was a strong inhibitor of HPV-16 long control region (LCR) activity in two human cervical carcinoma cell lines. The effect of IFN-gamma was dose dependent. We investigated whether the effect of IFN-gamma on HPV-16 LCR could involve the inhibition of the CREB-binding protein (CBP)/p300 family of transcriptional coactivators. In support of this model, we demonstrated by transfection experiments that a 12S E1A mutant (RG2), which interacts poorly with p300 and CBP in comparison to wild-type E1A, was less able to repress human papillomavirus (HPV) 16 long control region (LCR) than wild-type E1A. More important, overexpression of p300 was able to increase the HPV-16 LCR activity and to overcome inhibition by IFN-gamma. Finally, we demonstrated that p300 could cooperate with c-jun to activate HPV-16 LCR. According to our results, IFN-gamma might inhibit HPV-16 LCR transcription by activating the signal transducer and activator of transcription 1alpha, which in turn might compete for p300/CBP binding with specific transcription factors involved in LCR activation.Journal ArticleResearch Support, Non-U.S. Gov'tFLWINinfo:eu-repo/semantics/publishe

Progressive multifocal leukoencephalopathy in a case of acquired immune deficiency syndrome

The case of a 40-year-old homosexual male with A.I.D.S. (Acquired Immune Deficiency Syndrome) and P.M.L. (Progressive Multifocal Leukoencephalopathy) is described. The importance of a brain biopsy for diagnostic procedures, especially in the case of a patient with A.I.D.S. is stressed. The diagnosis P.M.L. has been made by means of light- and electronic microscopical examination, and the presence of JCV-DNA in the brain tissue has been confirmed by dot hybridization. Various antiviral treatments did not show any effect on the course of the P.M.

Characterization of the nuclear polyhedrosis virus DNA of Adoxophyes orana and of Barathra brassicae

Circular double-stranded DNA was isolated from nuclear polyhedrosis virus (NPV) of Adoxophyes orana (virus particles singly embedded in the polyhedral matrix) and NPV of Barathra brassicae (virus particles multiply embedded in the polyhedral matrix), and some of their physical properties were determined. The molecular weights of A. orana and B. brassicae NPV-DNA, 6.7 x 107 and 8.9 x 107, respectively, were determined by electron microscopy and by renaturation kinetics analysis. The latter analysis also showed that both genomes do not contain repetitive sequences. Absence of homology between DNA of these two viruses was shown by competition hybridization of A. orana NPV-DNA with B. brassicae NPV-DNA. Analysis of these DNAs with the restriction endonuclease EcoRI confirmed that they are different. The buoyant densities in CsCl of A. orana NPV-DNA and of B. brassicae NPV-DNA, 1.694 and 1.696 g/cm3, respectively, are consistent with (G + C) contents of 34.5 and 37%, respectively, as determined by thermal denaturation