Stefan Schwartz research group

Human papillomavirus type 16 life-cycle in mucosal epithelium, Naoko Kajitani©

We are investigating how carcinogenic human papillomaviruses (HPV) and human herpes viruses (HSV1, HSV2 and VZV) regulate gene expression at at the level of RNA processing. For HPV we study regulation of expression of the replication factors E1 and E2 and the E6 and E7 oncogenes while for HSV and VZV we focus on the latency associated RNAs named LAT and VLT, respectively.

Human papillomaviruses and human herpes viruses: ancient and common viruses with elaborate gene regulation

Human papillomaviruses

Human papillomavirus (HPV) infections cause more than 600.000 cases of cervical cancer each year in the world (>500 cases in Sweden). HPV16 is the most common cancer-associated HPV type. The majority of all HPV16 infections is cleared by the host but a fraction persists and may cause cancer.

During the viral life-cycle, two HPV proteins termed E1 and E2 hijack the cellular DNA polymerase to replicate the viral genome. The HPV E6 and E7 proteins stimulate cell division and prevent apoptosis to ensure a continued supply of cellular DNA polymerase for HPV replication. The HPV infection may in rare cases get stuck in a stage of continuous E6 and E7 expression, cell division and inabilty to undergo apoptosis. Under such conditions, the infection may progress to cancer. Here we investigate how expression of the HPV E6 and E7 oncogenes is regulated at the level of RNA splicing and how E6 and E7 mRNA splicing is controlled during carcinogenesis. We have identified RNA elements that control E6/E7 mRNA splicing and E1/E2 mRNA splicing (see Figures).

For a recent summary of papillomavirus gene regulation and RNA processing, including our own results, please have a look at the following review article.

Regulation of E6/E7 mRNA splicing

Regulation of E1/E2 mRNA splicing

Human herpes viruses

Some human herpesviruses (HHV) invariably infect the nervous system and persist for life in a silent aka latent stage (HSV1, HSV2 and VZV). These infections are recurrently activated during life and may under such occasions damage cells and even cause serious disease including meningoencephalitis. Recently, evidence is accumulating that herpesviruses also contribute to neurodegenerative diseases, such as Alzheimers disease and multiple sclerosis. RNA splicing plays a major role in expression of the viral latency associated RNAs that control viral latency and reactivation. Here we investigate how expression of the latency associated RNAs LAT in HSV and VLT in VZV are regulated at the level of RNA splicing (see Figures). Our research will enhance our understanding of herpesvirus latency and reactivation.