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Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals

1
IRCSS San Raffaele Pisana, Microbiology of Chronic Neuro-degenerative Pathologies, 00163 Rome, Italy
2
Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00185 Rome, Italy
3
Department of Biochemical Sciences “A. Rossi Fanelli”, “Sapienza” University of Rome, 00185 Rome, Italy
4
Laboratory of Clinical Microbiology and Virology, Polyclinic Tor Vergata Foundation, 00133 Rome, Italy
5
Infectious Diseases Clinic, Policlinic Tor Vergata, 00133 Rome, Italy
6
Department of System Medicine, Tor Vergata University of Rome, 00133 Rome, Italy
7
Department of Public Health and Infectious Diseases, Institute Pasteur, Cenci-Bolognetti Foundation, Sapienza University of Rome, 00185 Rome, Italy
8
IRCCS San Raffaele Pisana, Telematic University, 00163 Rome, Italy
9
Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, 9037 Tromsø, Norway
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Equal senior-author contribution.
Int. J. Mol. Sci. 2020, 21(21), 7998; https://doi.org/10.3390/ijms21217998
Received: 22 September 2020 / Revised: 20 October 2020 / Accepted: 24 October 2020 / Published: 27 October 2020
(This article belongs to the Section Molecular Microbiology)
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. View Full-Text
Keywords: Merkel cell polyomavirus (MCPyV); viral protein 1 (VP1); amino-acids mutation; protein structural organization; HIV+ individuals; A549 culture system Merkel cell polyomavirus (MCPyV); viral protein 1 (VP1); amino-acids mutation; protein structural organization; HIV+ individuals; A549 culture system
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MDPI and ACS Style

Prezioso, C.; Bianchi, M.; Obregon, F.; Ciotti, M.; Sarmati, L.; Andreoni, M.; Palamara, A.T.; Pascarella, S.; Moens, U.; Pietropaolo, V. Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. Int. J. Mol. Sci. 2020, 21, 7998. https://doi.org/10.3390/ijms21217998

AMA Style

Prezioso C, Bianchi M, Obregon F, Ciotti M, Sarmati L, Andreoni M, Palamara AT, Pascarella S, Moens U, Pietropaolo V. Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. International Journal of Molecular Sciences. 2020; 21(21):7998. https://doi.org/10.3390/ijms21217998

Chicago/Turabian Style

Prezioso, Carla, Martina Bianchi, Francisco Obregon, Marco Ciotti, Loredana Sarmati, Massimo Andreoni, Anna T. Palamara, Stefano Pascarella, Ugo Moens, and Valeria Pietropaolo. 2020. "Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals" International Journal of Molecular Sciences 21, no. 21: 7998. https://doi.org/10.3390/ijms21217998

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