Human papillomavirus gene expression is controlled by host cell splicing factors.

HPVs (human papillomaviruses) infect stratified epithelia and cause a variety of lesions ranging from benign warts to invasive tumours. The virus life cycle is tightly linked to differentiation of the keratinocyte it infects: papillomaviruses modulate host gene expression to ensure efficient virus replication. For example, the viral transcription factor E2 can directly up-regulate, in an epithelial differentiation-dependent manner, cellular SRSFs [SR (serine/arginine-rich) splicing factors] that control constitutive and alternative splicing. Changes in alternative splicing and the mechanisms controlling this for viral mRNAs have been the subject of intense exploration. However, to date experiments have only been carried out in model systems because the genetic systems suitable for studying alternative splicing of viral RNAs in the context of the virus life cycle are relatively recent and technically challenging. Now using these life cycle-supporting systems, our laboratory has identified SR proteins as important players in differentiation-dependent regulation of HPV gene expression. Better understanding of the role of cellular factors in regulating the virus life cycle is needed as it may help development of novel diagnostic approaches and antiviral therapies in the future.