circular RNA in viral oncogenesis

Identification and roles of viral circular RNAs in cancer and cell proliferation induced by lymphotropic herpesviruses and retroviruses (Collaboration with B. MUYLKENS UNamur and B. Dewals ULg)

CircRNAs take part in the regulation of gene expression at the transcriptional, post-transcriptional, translational and post-translational levels. Recently, circRNAs have been discovered to be encoded by few DNA or RNA viruses and likely mediate key functions during viral infections. However, the mechanisms by which viral circRNAs are involved in the regulation of viral replication, latency and/or virus-induced lymphomagenesis remain largely unknown. Herpesviruses and retroviruses are both capable of latency and use this infection program as a mode of persistence. Some of these latent infections are associated with reprogramming the cells hosting the latent virus and may initiate cancer development as observed in human infected with HTLV-1 (Human T cell leukemia/lymphoma virus type 1), in cattle infected with BLV (Bovine Leukemia Virus), in chicken infected with Marek’s disease virus-1 (MDV-1) and in cattle infected with Alcelaphine herpesvirus 1 (AlHV-1). These four viruses share two common features, first their tropism for lymphocytes and second their capacity to trigger lymphoproliferation associated with latent infection. In this context, the present project aims at identifying the expression of viral circRNAs in relevant animal and human lymphotropic viruses and to investigate how they regulate cell proliferation, viral lytic replication, latency and tumorigenesis. First, the viral cirRNAome will be established in several members belonging to herpesviruses or retroviruses family. Then, we will characterize these circular transcripts by exploring the function of specific circRNA candidates and determining their potential involvement in controlling the viral replication cycle and/or the host cell proliferation. Viral circRNAs encoded by retroviruses have not been published to date. However, our collaboration with the laboratory of Pr. Benoit Muylkens has enabled the identification of several circRNAs expressed from BLV. BLV is a relevant model to study retrovirus-induced leukemia and sharing several features with HTLV1 which will also be studied in this project.

This collaboration was reported in the FNRS/F.R.S. News 127 of March 2023. (see page 38)