Epstein-Barr virus SM protein.

The protein products of the Epstein-Barr virus (EBV) BMLF1 open reading frame have been characterized in the early productive cycle in B95-8 and Akata cells. The SM protein derived from the spliced RNA joining BSLF2 to BMLF1 is much the most abundant protein. SM is a phosphoprotein in EBV-infected cells and can be phosphorylated in vitro with casein kinase II (CKII). Computer analysis of the SM protein sequence showed a C terminal section of SM to be related to genome positional homologues of four other herpesviruses and revealed consensus CKII sites near the N termini of the EBV SM protein, the herpes simplex virus (HSV) ICP27 protein and the herpesvirus saimiri (HVS) open reading frame 57 protein. Site-directed mutagenesis of the consensus CKII site in EBV SM greatly reduced the in vitro phosphorylation of SM by CKII. The mechanism of transactivation by BMLF1 proteins has been controversial but SM was shown to transactivate gene expression from a CAT reporter construct by increasing the amount of cytoplasmic CAT mRNA. Mutagenesis of the CKII site in SM made no difference to the transactivation in this transient transfection assay.

Human papillomaviruses, tumour suppressor genes and cervical cancer.

There is now a considerable body of evidence that links HPV infection with anogenital squamous carcinoma, particularly for specific 'high risk' HPV types (HPV16 and 18) and invasive carcinoma of the cervix. Recent advances in the molecular study of these viruses have elucidated some potential mechanisms by which they may contribute to the development of these diseases. In this review we concentrate on the interactions of 2 of the HPV encoded proteins, E6 and E7, with cellular tumour suppressor gene products. We provide a model of how these interactions may be important in tumourigenesis and draw together current knowledge of this exciting and rapidly evolving field.