Lymphoma outbreak in a GASH:Sal hamster colony

Muñoz, Luis J.; Ludeña, Dolores; Gedvilaitė, Alma; Žvirblienė, Aurelija; Jandrig, Burkhard; Voronkova, Tatyana; Ulrich, Rainer G.; López, Dolores E.

doi:10.1007/s00705-013-1737-0

Cited by 13 publications

(20 citation statements)

References 18 publications

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“…The insertion of four nucleotides in noncoding region between LTag and VP1 genes in BVPyV (KS/13/999) genome was also determined. This is in line with previous studies indicating that the highest level of variation is common for noncoding regions of PyVs [ 73 , 75 ].…”

Section: Resultssupporting

confidence: 93%

Identification of Two Novel Members of the Tentative Genus Wukipolyomavirus in Wild Rodents

et al. 2015

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Two novel polyomaviruses (PyVs) were identified in kidney and chest-cavity fluid samples of wild bank voles (Myodes glareolus) and common voles (Microtus arvalis) collected in Germany. All cloned and sequenced genomes had the typical PyV genome organization, including putative open reading frames for early regulatory proteins large T antigen and small T antigen on one strand and for structural late proteins (VP1, VP2 and VP3) on the other strand. Virus-like particles (VLPs) were generated by yeast expression of the VP1 protein of both PyVs. VLP-based ELISA and large T-antigen sequence-targeted polymerase-chain reaction investigations demonstrated signs of infection of these novel PyVs in about 42% of bank voles and 18% of common voles. In most cases only viral DNA, but not VP1-specific antibodies were detected. In additional animals exclusively VP1-specific antibodies, but no viral DNA was detected, indicative for virus clearance. Phylogenetic and clustering analysis including all known PyV genomes placed novel bank vole and common vole PyVs amongst members of the tentative Wukipolymavirus genus. The other known four rodent PyVs, Murine PyV and Hamster PyV, and Murine pneumotropic virus and Mastomys PyV belong to different phylogenetic clades, tentatively named Orthopolyomavirus I and Orthopolyomavirus II, respectively. In conclusion, the finding of novel vole-borne PyVs may suggest an evolutionary origin of ancient wukipolyomaviruses in rodents and may offer the possibility to develop a vole-based animal model for human wukipolyomaviruses.

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Section: Resultssupporting

confidence: 93%

Identification of Two Novel Members of the Tentative Genus Wukipolyomavirus in Wild Rodents

et al. 2015

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“…For production of HPyV12-derived VP1 VLPs in yeast, we used both the native virus gene sequence (HPyV12 VP1n 380 ) and a version that was codon-optimized for S. cerevisiae expression (HPyV12 VP1s 380 ), synthesized by GenScript. Both VP1-encoding genes were cloned into the expression vector, pFX7 [ 25 ], and transformed into the yeast strain, AH22-214. Expression of HPyV12 VP1 380 , analyzed using SDS-PAGE, was low using both versions of the gene (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…MCPyV has gained the most attention due to its link with a rare and aggressive malignant human skin cancer, Merkel cell carcinoma, in the elderly and chronically immunosuppressed individuals [ 19 ]. It has been shown that hamster polyomavirus (HaPyV) is responsible for the high incidence of lymphomas in a colony of genetic audiogenic seizure hamsters (GASH:Sal) [ 25 ]. Moreover, proteins encoded by some PyVs have transforming ability in cell culture and tumorigenic activity in animals [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Production of recombinant VP1-derived virus-like particles from novel human polyomaviruses in yeast

et al. 2015

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BackgroundEleven new human polyomaviruses (HPyVs) have been identified in the last decade. Serological studies show that these novel HPyVs sub-clinically infect humans at an early age. The routes of infection, entry pathways, and cell tropism of new HPyVs remain unknown. VP1 proteins of polyomaviruses can assembly into virus-like particles (VLPs). As cell culturing systems for HPyV are currently not available, VP1-derived VLPs may be useful tools in basic research and biotechnological applications.ResultsRecombinant VP1-derived VLPs from 11 newly identified HPyVs were efficiently expressed in yeast. VP1 proteins derived from Merkel cell polyomavirus (MCPyV), trichodysplasia spinulosa-associated polyomavirus (TSPyV), and New Jersey polyomavirus (NJPyV) self-assembled into homogeneous similarly-sized VLPs. Karolinska Institutet polyomavirus (KIPyV), HPyV7, HPyV9, HPyV10, and St. Louis polyomavirus (STLPyV) VP1 proteins formed VLPs that varied in size with diameters ranging from 20 to 60 nm. Smaller-sized VLPs (25–35 nm in diameter) predominated in preparations from Washington University polyomavirus (WUPyV) and HPyV6. Attempts to express recombinant HPyV12 VP1-derived VLPs in yeast indicate that translation of VP1 might start at the second of two potential translation initiation sites in the VP1-encoding open reading frame (ORF). This translation resulted in a 364-amino acid-long VP1 protein, which efficiently self-assembled into typical PyV VLPs. MCPyV-, KIPyV-, TSPyV-, HPyV9-, HPyV10-, and HPyV12-derived VLPs showed hemagglutination (HA) assay activity in guinea pig erythrocytes, whereas WUPyV-, HPyV6-, HPyV7-, STLPyV- and NJPyV-derived VP1 VLPs did not.ConclusionsThe yeast expression system was successfully utilized for high-throughput production of recombinant VP1-derived VLPs from 11 newly identified HPyVs. HPyV12 VP1-derived VLPs were generated from the second of two potential translation initiation sites in the VP1-encoding ORF. Recombinant VLPs produced in yeast originated from different HPyVs demonstrated distinct HA activities and may be useful in virus diagnostics, capsid structure studies, or investigation of entry pathways and cell tropism of HPyVs until cell culture systems for new HPyVs are developed.

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“…However, it remains possible that the apparently VP2-independent infectious route is also relevant to pathobiology. A recent publication from Muñoz and colleagues documents an outbreak of hamster polyomavirus (HaPyV)-induced lymphoma [59]. Interestingly, most HaPyV genomes isolated from lymphoma cells were found to have deletion mutations encompassing the N-terminus of VP2 and, in one instance the N-terminus of VP3 as well.…”

Section: Discussionmentioning

confidence: 99%

The Merkel Cell Polyomavirus Minor Capsid Protein

Schowalter

Buck

2013

PLoS Pathog

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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.

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Lymphoma outbreak in a GASH:Sal hamster colony

Cited by 13 publications

References 18 publications

Identification of Two Novel Members of the Tentative Genus Wukipolyomavirus in Wild Rodents

Identification of Two Novel Members of the Tentative Genus Wukipolyomavirus in Wild Rodents

Production of recombinant VP1-derived virus-like particles from novel human polyomaviruses in yeast

The Merkel Cell Polyomavirus Minor Capsid Protein

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