A Comprehensive Analysis of Replicating Merkel Cell Polyomavirus Genomes Delineates the Viral Transcription Program and Suggests a Role for mcv-miR-M1 in Episomal Persistence
MCPyV is a recently discovered human polyomavirus that is likely to cause the majority of cases of Merkel cell carcinoma (MCC), a rare but highly aggressive skin cancer. While much research has been focused on understanding transforming functions of MCPyV gene products, owing to the lack of fully permissive replication systems, the natural lifecycle of the virus is poorly understood. Using high-throughput analyses, here we have interrogated a semi-permissive replication system to study the viral transcription program and elucidate the functions of the viral microRNA (miRNA) mcv-miR-M1. We find that, similar to other polyomavirus miRNAs, mcv-miR-M1 has the ability to negatively regulate expression of viral gene products required for viral DNA replication. Unexpectedly, however, we also observe that mcv-miR-M1 augments long-term episomal persistence of MCPyV genomes. Given that MCPyV establishes persistent infections in the majority of healthy human adults, our observations shed new light on the mechanisms that may be employed by this tumor virus to mount a lifelong chronic infection of its host.
Vyšlo v časopise:
A Comprehensive Analysis of Replicating Merkel Cell Polyomavirus Genomes Delineates the Viral Transcription Program and Suggests a Role for mcv-miR-M1 in Episomal Persistence. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1004974
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Research Article
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https://doi.org/10.1371/journal.ppat.1004974
Souhrn
MCPyV is a recently discovered human polyomavirus that is likely to cause the majority of cases of Merkel cell carcinoma (MCC), a rare but highly aggressive skin cancer. While much research has been focused on understanding transforming functions of MCPyV gene products, owing to the lack of fully permissive replication systems, the natural lifecycle of the virus is poorly understood. Using high-throughput analyses, here we have interrogated a semi-permissive replication system to study the viral transcription program and elucidate the functions of the viral microRNA (miRNA) mcv-miR-M1. We find that, similar to other polyomavirus miRNAs, mcv-miR-M1 has the ability to negatively regulate expression of viral gene products required for viral DNA replication. Unexpectedly, however, we also observe that mcv-miR-M1 augments long-term episomal persistence of MCPyV genomes. Given that MCPyV establishes persistent infections in the majority of healthy human adults, our observations shed new light on the mechanisms that may be employed by this tumor virus to mount a lifelong chronic infection of its host.
Zdroje
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