Primary infections with human polyomaviruses (HPyVs) are ubiquitous but asymptomatic, and generally occur during early childhood with seroprevalence rates ranging from 20% to 99%. HPyVs were isolated from a variety of sources implicating horizontal transmission by direct contact, respiratory aerosols and/or fecal-oral route. Primary infection is followed by lifelong latency that is controlled by cellular and humoral immune surveillance. Impairment of this immune control by a variety of perturbations, including chronic diseases, primary or acquired immunodeficiency, immunosuppressive drugs, or transplantation, may lead to a broad spectrum of pathologies ranging from inflammatory to neoplastic. We are interested in studying cellular pathways involved in polyomavirus pathogenesis using oncogenic Merkel cell polyomavirus (MCV) and other polyomaviruses that are known to be associated with non-neoplastic diseases in immunocompromised patients (1, 2).
High-throughput analysis of the transcriptome and proteome provides means to explore and determine diagnostic, prognostic, and therapeutic biomarkers in the context of infectious diseases. We are interested in generating and characterizing a large collection of SARS-CoV2 viral strains and employ next generation sequencing (NGS) methods to analyze viral and cellular transcriptome (3).
Circular RNAs (circRNA) are formed by backsplicing of linear RNA and can be exonic and/or intronic. These molecules have been found to be expressed in almost all cells, sometimes at higher levels than their corresponding linear forms. Due to their covalently joined circular nature, circRNAs are resistant to exonucleases and are therefore highly stable. KSHV and EBV circRNAs were recently identified as a new class of viral transcripts expressed in gamma herpesvirus-related tumors (4). These molecules might play a critical role in infection and oncogenesis, and thus could be a target for precision therapies. We are interested in identification and characterization of viral circRNAs, as well as assessing their importance for pathogenesis and potential as biomarkers.
1. Toptan T, Yousem SA, Ho J, Matsushima Y, Stabile LP, Fernandez-Figueras MT, Bhargava R, Ryo A, Moore PS, Chang Y. 2016. Survey for human polyomaviruses in cancer. JCI Insight 1(2): e85562.
2. Rigatti LH*, Toptan T*, Newsome JT, Moore PS, Chang Y. 2016. Identification and Characterization of Novel Rat Polyomavirus 2 in a Colony of X-SCID Rats by P-PIT assay. mSphere 1(6), e00334-16.
3. Toptan T, Hoehl S, Westhaus S, Bojkova D, Berger A, Rotter B, Hoffmeier K, Ciesek S, Widera M. 2020. Optimized qRT-PCR approach for the detection of intra- and extra-cellular SARS-CoV-2 RNAs.
bioRxiv 2020.04.20.052258; doi: https://doi.org/10.1101/2020.04.20.052258
4. Toptan T, Abere B, Nalesnik MA, Swerdlow SH, Ranganathan S, Lee N, Shair KH, Moore PS, Chang Y. 2018. Circular DNA tumor viruses make circular RNAs. Proc Natl Acad Sci USA doi:10.1073/pnas.1811728115.