Merkel Cell Polyomavirus - Discovery and Characterization of MCV

Discovery and Characterization of MCV

Yuan Chang and Patrick S. Moore, who discovered Kaposi's sarcoma-associated herpesvirus in 1994, used the novel high-throughput sequencing technique of digital transcriptome subtraction (DTS) to search for the presence of a virus in Merkel cell tumors. In this method, all mRNAs from a tumor are converted into cDNAs and sequenced to a depth likely to sequence a viral cDNA if it is present. The sequences are then compared with the human genome and all human sequences are "subtracted" to leave a group of sequences that are most likely nonhuman. When this was performed on four cases of Merkel cell carcinoma, one cDNA was found that was similar to sequences of known polyomaviruses but clearly distinct enough that it could be shown to be a new virus. Genetic sequences from nearly 400,000 mRNAs were analyzed for the study. Once the virus was found, Feng and coworkers quickly determined that infected Merkel cell carcinomas have the virus in an integrated monoclonal pattern and only found 8-16% of tissues taken from patients without MCC were positive for the virus. This was quickly confirmed by studies of MCC patients from around the world, including evidence for monoclonal integration of the virus in these tumors.