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. 2015 Jan;89(1):857-62.
doi: 10.1128/JVI.02328-14. Epub 2014 Oct 15.

Malawi polyomavirus is a prevalent human virus that interacts with known tumor suppressors

Christian Berrios  1 , Joonil Jung  2 , Blake Primi  3 , Michael Wang  4 , Chandrasekhar Pedamallu  5 , Fujiko Duke  5 , Christina Marcelus  6 , Jingwei Cheng  7 , Robert L Garcea  3 , Matthew Meyerson  8 , James A DeCaprio  9
Affiliations

Malawi polyomavirus is a prevalent human virus that interacts with known tumor suppressors

Christian Berrios et al. J Virol. 2015 Jan.

Abstract

Malawi polyomavirus (MWPyV) is a recently identified human polyomavirus. Serology for MWPyV VP1 indicates that infection frequently occurs in childhood and reaches a prevalence of 75% in adults. The MWPyV small T antigen (ST) binds protein phosphatase 2A (PP2A), and the large T antigen (LT) binds pRb, p107, p130, and p53. However, the MWPyV LT was less stable than the simian virus 40 (SV40) LT and was unable to promote the growth of normal cells. This report confirms that MWPyV is a widespread human virus expressing T antigens with low transforming potential.

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Figures

FIG 1
FIG 1
Age-specific seroprevalence determined in a Denver, CO, USA, study population (n = 500) for MWPyV. (A) Determination of inflection points for MWPyV VP1 antigens assayed using the VP1-GST ELISA. Two best-fit functions, one sixth-order (A) and one third-order (B) polynomial, were derived from the data using Microsoft Excel. The inflection points were calculated by setting the second derivative of the corresponding function to zero. The average of the two inflection point (Average IP) values (average = 0.677) was the final assigned cutoff value. All absorbance values above that were considered to represent seropositivity. (B) MWPyV age-specific seroprevalence from 500 serum samples tested in triplicate, indicating an age-related increase in seropositivity.
FIG 2
FIG 2
MWPyV T antigens bind to human tumor suppressors. (A) U-2OS cells stably expressing CTAP-GFP (CT-GFP), NTAP-SV40 LT (NT-SV40 LT), CT-MWPyV LT, CT-SV40 ST, and CT-MWPyV ST were transfected with the indicated V5-tagged constructs of PP2A-Aα, pRb, and p53 or with a control EGFP-expressing vector. After an 8-h treatment with 10 μM MG-132, cells were lysed and immunoprecipitated with either HA antibody-conjugated beads (IP: HA) or V5 antibody-conjugated beads (IP: V5). Blotting with HA (IB: HA) or V5 (IB: V5) was performed to detect IP of the CTAP/NTAP constructs or coimmunoprecipitation of the PP2A-Aα, pRb, and p53 constructs, respectively. Vinculin-specific antibody was used as a loading control. (B) U-2OS cells stably expressing CT-GFP, CT-MWPyV LT, and CT-MWPyV LT.E109K were transfected with the indicated V5-tagged constructs of pRb, p107, and p130 or with a control EGFP-expressing vector. After MG-132 treatment, cells were lysed and immunoprecipitated as described for panel A. Actin-specific antibody was used as a loading control.
FIG 3
FIG 3
MWPyV LT is quickly degraded after cycloheximide treatment and fails to promote growth of IMR-90 human fibroblasts. (A) U-2OS cells stably expressing CTAP-GFP (CT-GFP), CT-MWPyV LT, or NTAP-SV40 LT (NT-SV40 LT) were treated with DMSO, 50 μg/ml cycloheximide (CHX), or 10 μM MG-132 and harvested at the indicated hours posttreatment. Cells were lysed and immunoblotted with antibodies against p53, HA, or actin. (B) IMR-90 cells expressing vector, SV40, MCPyV, and MWPyV LT in 15% FBS were seeded and grown for 12 days. (C) IMR-90 cells expressing vector, SV40, MCPyV, and MWPyV LT in 1% FBS were seeded and grown for 14 days. Cell density was determined by crystal violet staining followed by optical density measurement at 590 nm.
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References

    1. DeCaprio JA, Garcea RL. 2013. A cornucopia of human polyomaviruses. Nat Rev Microbiol 11:264–276. doi:10.1038/nrmicro2992. - DOI - PMC - PubMed
    1. Jiang M, Abend JR, Johnson SF, Imperiale MJ. 2009. The role of polyomaviruses in human disease. Virology 384:266–273. doi:10.1016/j.virol.2008.09.027. - DOI - PMC - PubMed
    1. van der Meijden E, Janssens RW, Lauber C, Bouwes Bavinck JN, Gorbalenya AE, Feltkamp MC. 2010. Discovery of a new human polyomavirus associated with trichodysplasia spinulosa in an immunocompromized patient. PLoS Pathog 6:e1001024. doi:10.1371/journal.ppat.1001024. - DOI - PMC - PubMed
    1. Feng H, Shuda M, Chang Y, Moore PS. 2008. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 319:1096–1100. doi:10.1126/science.1152586. - DOI - PMC - PubMed
    1. Rodig SJ, Cheng J, Wardzala J, DoRosario A, Scanlon JJ, Laga AC, Martinez-Fernandez A, Barletta JA, Bellizzi AM, Sadasivam S, Holloway DT, Cooper DJ, Kupper TS, Wang LC, DeCaprio JA. 2012. Improved detection suggests all Merkel cell carcinomas harbor Merkel polyomavirus. J Clin Invest 122:4645–4653. doi:10.1172/JCI64116. - DOI - PMC - PubMed

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