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New study sheds light on how MCV causes cancer

Researchers from the University of Pittsburgh have made a groundbreaking discovery regarding Merkel cell polyomavirus (MCV), a virus responsible for causing an aggressive skin called Merkel cell carcinoma. The study, published in the journal PNAS, delves into how MCV initiates DNA replication in host , a process essential for the virus to produce numerous copies of itself.

Co-senior authors, Dr. Patrick Moore and Dr. Yuan Chang, first identified MCV in 2008. While the virus is typically harmless, it can occasionally lead to Merkel cell carcinoma, a lethal form of skin cancer diagnosed in about 3,000 people annually in the U.S.

The research team used a C-trap instrument and the SMADNE technique to study MCV replication in unprecedented detail. Unlike previous static images, the C-trap allowed the researchers to observe binding to a single DNA molecule in .

During normal , DNA replication involves helicases, proteins that unzip the DNA double helix into single strands to facilitate further steps. This process consumes cellular energy in the form of ATP and is meticulously regulated by the cell. However, when a virus takes over the cell's DNA replication machinery, it can replicate hundreds of times, a process termed “unlicensed” replication. This uncontrolled replication is more error-prone and can lead to cancer, as certain mutations might be inserted into the host's genome.

The researchers discovered that MCV's helicase functions differently than anticipated. Instead of forming sleeves around the DNA, the viral helicase directly separates the DNA molecule. Moreover, it can do this repeatedly without utilizing ATP, enabling the virus to outcompete normal cellular replication.

The findings have significant implications for understanding cancer-causing viruses. By gaining insights into how MCV replicates, researchers hope to develop new therapeutics or for cancers caused by viral infections. The team plans to extend their research to study other cancer-causing viruses, like human papillomavirus (HPV) and Kaposi sarcoma herpes virus, to further understand viral replication mechanisms and develop targeted antiviral medications or vaccines.

The study involved collaboration with researchers from various institutions, including the University of Pennsylvania and Tsinghua University.

Source: University of Pittsburgh

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