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Updated: May 8, 2026
Merkel Cell Polyomavirus Infection and Detection
Published on: February 7, 2019
The Merkel cell polyomavirus minor capsid protein
Rachel M Schowalter1, Christopher B Buck
1Tumor Virus Molecular Biology Section, Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
Abstract:
The surface of polyomavirus virions is composed of pentameric knobs of the major capsid protein, VP1. In previously studied polyomavirus species, such as SV40, two interior capsid proteins, VP2 and VP3, emerge from the virion to play important roles during the infectious entry process. Translation of the VP3 protein initiates at a highly conserved Met-Ala-Leu motif within the VP2 open reading frame. Phylogenetic analyses indicate that Merkel cell polyomavirus (MCV or MCPyV) is a member of a divergent clade of polyomaviruses that lack the conserved VP3 N-terminal motif. Consistent with this observation, we show that VP3 is not detectable in MCV-infected cells, VP3 is not found in native MCV virions, and mutation of possible alternative VP3-initiating methionine codons did not significantly affect MCV infectivity in culture. In contrast, VP2 knockout resulted in a >100-fold decrease in native MCV infectivity, despite normal virion assembly, viral DNA packaging, and cell attachment. Although pseudovirus-based experiments confirmed that VP2 plays an essential role for infection of some cell lines, other cell lines were readily transduced by pseudovirions lacking VP2. In cell lines where VP2 was needed for efficient infectious entry, the presence of a conserved myristoyl modification on the N-terminus of VP2 was important for its function. The results show that a single minor capsid protein, VP2, facilitates a post-attachment stage of MCV infectious entry into some, but not all, cell types.
Insights
Merkel cell polyomavirus (MCV) VP3 is not essential for infection, unlike in other polyomaviruses. The minor capsid protein VP2 is crucial for MCV entry into specific cell types.
Area of Science:
- Virology
- Molecular Biology
- Structural Biology
Background:
- Polyomavirus virions feature VP1 major capsid protein knobs.
- VP2 and VP3 are internal capsid proteins crucial for infectious entry in studied species like SV40.
- VP3 translation initiates from a conserved motif within the VP2 open reading frame.
Purpose of the Study:
- To investigate the roles of VP2 and VP3 proteins in Merkel cell polyomavirus (MCV) infection.
- To determine if MCV encodes a functional VP3 protein.
- To elucidate the specific functions of VP2 during MCV entry.
Main Methods:
- Phylogenetic analysis of MCV clade polyomaviruses.
- Detection of VP3 in MCV-infected cells and virions.
- Mutation analysis of potential VP3 initiation sites.
- VP2 knockout and pseudovirus-based infectivity assays.
- Assessment of VP2 myristoylation modification.
Main Results:
- MCV lacks the conserved VP3 N-terminal motif and VP3 is undetectable in infected cells and virions.
- VP3 mutations did not significantly impact MCV infectivity.
- VP2 knockout reduced MCV infectivity by over 100-fold, without affecting virion assembly or DNA packaging.
- VP2 is essential for MCV entry into some cell lines, but not others.
- N-terminal myristoylation of VP2 is critical for its function in specific cell types.
Conclusions:
- Merkel cell polyomavirus (MCV) does not produce a functional VP3 protein.
- The minor capsid protein VP2 plays a critical, albeit cell-type-specific, role in post-attachment MCV entry.
- VP2's conserved N-terminal myristoylation is important for its function in facilitating MCV infection.
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