Control of Host Gene Expression by a Herpesvirus Transcription Factor
Herpes simplex virus and other alpha-herpesviruses encode a transcription factor, VP16, able to activate expression of genes containing its binding site (TAATGARAT) in the promoter region. VP16 protein is present inside the infectious virion and it enters the host cell with the virus nucleocapsid. Once inside the cell, VP16 is able to cause the prompt expression of virus genes adjacent to its binding sites. I have examined the possibility that host gene expression may have the potential to be affected by the presence of VP16, a situation that could have important effects on alpha-herpesvirus replication. Bioinformatic methods were used to examine five human genome regions (each 16-73Mb in length) for the presence of genes with upstream TAATGARAT sequences. A total of fourteen characterized genes were identified indicating VP16 has the potential to activate their expression. The identified genes varied considerably in function, and did not appear to support a common theme or goal. The presence of an upstream TAATGARAT sequence was found to be well conserved in the homologous genes of chimpanzee where 11 of 14 homologous genes had upstream TAATGARAT’s. Conservation was poor, however, in three other species examined, mouse (2 of 14 genes), horse (2) and chicken (1). The observed pattern of conservation is interpreted to suggest that alpha-herpesviruses evolved the ability to benefit from expression of TAATGARAT-containing host genes and that this process was complete at or before the time chimpanzees and humans diverged evolutionarily (~7Mya).