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Updated: Dec 3, 2025
Merkel Cell Polyomavirus Infection and Detection
Published on: February 7, 2019
Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals
Carla Prezioso1,2, Martina Bianchi3, Francisco Obregon2
1IRCSS San Raffaele Pisana, Microbiology of Chronic Neuro-degenerative Pathologies, 00163 Rome, Italy.
Abstract:
Merkel cell polyomavirus (MCPyV) viral protein 1 (VP1) is the capsid protein that mediates virus attachment to host cell receptors and is the major immune target. Given the limited data on MCPyV VP1 mutations, the VP1 genetic variability was examined in 100 plasma and 100 urine samples from 100 HIV+ individuals. Sequencing of VP1 DNA in 17 urine and 17 plasma specimens, simultaneously MCPyV DNA positive, revealed that 27 samples displayed sequences identical to VP1 of MCC350 strain. VP1 from two urine specimens had either Thr47Ser or Ile115Phe substitution, whereas VP1 of one plasma contained Asp69Val and Ser251Phe substitutions plus deletion (∆) of Tyr79. VP1 DNA in the remaining samples had mutations encoding truncated protein. Three-dimensional prediction models revealed that Asp69Val, Ser251Phe, and Ile115Phe caused neutral effects while Thr47Ser and Tyr79∆ produced a deleterious effect reducing VP1 stability. A549 cells infected with urine or plasma samples containing full-length VP1 variants with substitutions, sustained viral DNA replication and VP1 expression. Moreover, medium harvested from these cells was able to infect new A549 cells. In cells infected by samples with truncated VP1, MCPyV replication was hampered. In conclusion, MCPyV strains with unique mutations in the VP1 gene are circulating in HIV+ patients. These strains display altered replication efficiency compared to the MCC350 prototype strain in A549 cells.
Insights
Merkel cell polyomavirus (MCPyV) VP1 gene mutations are present in HIV+ patients. These unique MCPyV strains show altered replication efficiency in A549 cells compared to the prototype strain.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Merkel cell polyomavirus (MCPyV) is a human polyomavirus associated with Merkel cell carcinoma.
- The viral protein 1 (VP1) is crucial for viral attachment and is a primary target for the immune system.
- Limited information exists regarding genetic variations in the MCPyV VP1 gene.
Purpose of the Study:
- To investigate the genetic variability of the MCPyV VP1 gene in human immunodeficiency virus-positive (HIV+) individuals.
- To analyze the impact of identified VP1 mutations on viral replication and protein stability.
Main Methods:
- VP1 DNA sequencing was performed on plasma and urine samples from 100 HIV+ individuals.
- Three-dimensional prediction models were used to assess the effects of mutations on VP1 stability.
- In vitro infection assays using A549 cells were conducted to evaluate viral replication.
Main Results:
- Several MCPyV strains with unique VP1 mutations, including substitutions and truncations, were identified in HIV+ patients.
- Specific mutations (Thr47Ser, Tyr79∆) were predicted to have deleterious effects on VP1 stability.
- Full-length VP1 variants with substitutions supported viral DNA replication and infectivity in A549 cells, while truncated VP1 hampered replication.
Conclusions:
- Circulating MCPyV strains in HIV+ patients exhibit significant genetic diversity in the VP1 gene.
- These VP1 mutations can alter viral replication efficiency and stability.
- Further research is needed to understand the clinical implications of these MCPyV variants.
