Clonal integration of a polyomavirus in human Merkel cell carcinoma.
H Feng, M Shuda, Y Chang, PS Moore. Science 2008 Feb
22;319(5866):1096-1100. "MCV sequences were detected in 8 of 10 (80%)
MCC tumors but only 5 of 59 (8%) control tissues from various body
sites and 4 of 25 (16%) control skin tissues. In six of eight
MCV-positive MCCs, viral DNA was integrated within the tumor genome in
a clonal pattern, suggesting that MCV infection and integration
preceded clonal expansion of the tumor cells."
Frequent detection of Merkel cell polyomavirus in human Merkel cell
carcinomas and identification of a unique deletion in the VP1 gene. A
Kassem, A Schöpflin, C Diaz, W Weyers, E Stickeler, M Werner, A
Zur Hausen. Cancer Res 2008 Jul 1;68(13):5009-5013. Merkel cell
polyomavirus was found in 30 of 39 (77%) Merkel cell carcinomas.
Merkel cell polyomavirus and Merkel cell carcinoma, France. V
Foulongne, N Kluger, O Dereure, N Brieu, B Guillot, M Segondy. Emerg
Infect Dis 2008 Sep;14(9):1491-1493. MCPyV was found in 8 of 9 patients
with MCC, of whom 2 were immunocompromised.; versus 0 of 15 patients
with diverse proliferative or inflammatory skin or mucosa lesions as
controls.
Merkel cell polyomavirus is more frequently present in North
American than Australian Merkel cell carcinoma tumors. KM Garneski, AH
Warcola, Q Feng, NB Kiviat, JH Leonard, P Nghiem. J Invest Dermatol
2009 Jan;129(1):246-248. "16 of 37 Merkel cell carcinoma tumor tissues
were positive for Merkel cell polyomavirus DNA (43%)," 11/16 (69%) from
North America, versus 5/21 (24%) from Australia. "We observed MCPyV in
5 of 8 primary tumors, 3 of 13 recurrences, 7 of 15 nodal metastases,
and in the single studied distant metastasis... The majority of
Australian samples were nodal metastases, whereas most North American
samples were primaries." Also, "most of the Australian tumor specimens
were collected in the 1990’s and most North American specimens were
collected after the year 2000." "MCPyV was not detected in any of the
normal skin DNA, but was present in 2 of 15 SCC tumors (13%)."
Ultrastructural proof of polyomavirus in Merkel cell carcinoma
tumour cells and its absence in small cell carcinoma of the lung. CT
Wetzels, JG Hoefnagel, JM Bakkers, HB Dijkman, WA Blokx, WJ Melchers.
PLoS ONE 2009;4(3):e4958. MCPyV was found in 2/5 Merkel cell carcinomas
and 0/10 small cell lung carcinomas.
Prevalence of Merkel cell polyomavirus in Merkel cell carcinoma. EJ
Duncavage, BA Zehnbauer, JD Pfeifer. Mod Pathol 2009 Apr;22(4):516-521.
41 cases of Merkel cell carcinoma (from 29 different patients). Of
these, 20 cases were primary cutaneous tumors, 4 were local
recurrences, and 17 were metastases. 22/29 (76%) were positive for
MCVPS1 (109 bp amplicon).
Merkel cell carcinoma of the skin: pathological and molecular
evidence for a causative role of MCV in oncogenesis. X Sastre-Garau, M
Peter, MF Avril, H Laude, J Couturier, F Rozenberg, A Almeida, F
Boitier, A Carlotti, B Couturaud, N Dupin. J Pathol 2009
May;218(1):48-56. "MCV DNA sequences were found in all ten cases of MCC
and in none of the 1241 specimens of other tumour types. Clonal
integration of MCV into the host genome was seen in all MCC cases and
was checked by FISH in one case. A recurrent pattern of conserved viral
sequences which encompassed the replication origin, the small tumour
(ST), and the 5' part of the large tumour (LT) antigen DNA sequences
was observed. Both ST and LT viral sequences were found to be
significantly expressed in all MCCs. Neither recurrent site of
integration nor alteration of cellular genes located near the viral
sequences was observed. The tight association of MCV with MCC, the
clonal pattern of MCV integration, and the expression of the viral
oncoproteins strongly support a causative role for MCV in the tumour
process."
Merkel cell polyomavirus strains in patients with merkel cell
carcinoma. A Touzé, J Gaitan, A Maruani, E Le Bidre, A
Doussinaud, C Clavel, A Durlach, F Aubin, S Guyétant, G Lorette,
P Coursaget. Emerg Infect Dis 2009 Jun;15(6):960-962. 21 of 32 (66%)
samples of Merkel cell carcinoma with suitable quality DNA were
positive for Merkel cell polyomavirus DNA. All 12 frozen samples were
positive versus only 9/20 (45%) of formalin-fixed and paraffin-embedded
samples. "MCPyV DNA was not detected for any of the 9 patients with
non-MCC neuroendocrine carcinomas," which were 5 small-cell lung
carcinomas, 3 well-differentiated intestinal carcinomas, and 1
high-grade neuroendocrine carcinoma of the cervix.
Array-CGH reveals recurrent genomic changes in Merkel cell carcinoma
including amplification of L-Myc. KG Paulson, BD Lemos, B Feng, N
Jaimes, PF Peñas, X Bi, E Maher, L Cohen, JH Leonard, SR
Granter, L Chin, P Nghiem. J Invest Dermatol 2009
Jun;129(6):1547-1555. "Tumors from 13 of 22 MCC patients had detectable
Merkel cell polyomavirus DNA, and these tumors had fewer genomic
deletions."
Clinical Factors Associated With Merkel Cell Polyomavirus Infection
in Merkel Cell Carcinoma. H Sihto, H Kukko, V Koljonen, R Sankila, T
Böhling, H Joensuu. J Natl Cancer Inst 2009 Jul 1;101(13):938-45.
79.8 % of 114 patients with Merkel cell carcinoma in Finland
were positive for Merkel cell polyomavirus DNA."Compared with MCPyV
DNA-negative cancers, MCPyV DNA-positive cancers were more often
located in a limb (40.7% vs 8.7%, P = .015) and less frequent in
patients who had regional nodal metastases at diagnosis (6.6% vs 21.7%,
P = .043). Patients with MCPyV DNA-positive tumors had better overall
survival than those with MCPyV DNA-negative tumors (5-year survival:
45.0% vs 13.0%, respectively; P < .001, two-sided log-rank test)."
Merkel cell polyomavirus sequences are frequently detected in
nonmelanoma skin cancer of immunosuppressed patients. A Kassem, K
Technau, AK Kurz, D Pantulu, M Löning, G Kayser, E Stickeler, W
Weyers, C Diaz, M Werner, D Nashan, A Zur Hausen. Int J Cancer 2009 Jul
15;125(2):356-361. 56 nonmelanoma skin cancers (squamous cell
carcinoma, basal cell carcinoma, and Bowen's disease) from 11
immunosuppressed patients and 147 NMSCs of 125 immunocompetent
patients; normal skin and 89 colorectal cancers as comparison. "MCPyV
specific sequences were significantly more frequently found in NMSC of
immunosuppressed patients compared to immunocompetent patients (p <
0.001). In particular BD and BCC revealed a significant increased
association of MCPyV of immunosuppressed patients (p = 0.002 and p =
0.006). Forty-seven of 147 (32%) sporadic NMSC were MCPyV positive. Interestingly,
37.5% (36/96) of sporadic BCC of immunocompetent patients were MCPyV
positive. No MCPyV was detected within normal skin and only 3
out of 89 of additionally tested colorectal cancers were MCPyV
positive."
Clinical factors associated with Merkel cell polyomavirus infection
in Merkel cell carcinoma. H Sihto, H Kukko, V Koljonen, R Sankila, T
Böhling, H Joensuu. J Natl Cancer Inst 2009 Jul 1;101(13):938-945.
114 Merkel cell carcinoma tissue samples in Finland from 1979 to 2004.
MCPyV DNA was present in 91 carcinomas (79.8%), and positive tumors
were more often located in a limb.
Merkel cell polyomavirus expression in merkel cell carcinomas and
its absence in combined tumors and pulmonary neuroendocrine carcinomas.
KJ Busam, AA Jungbluth, N Rekthman, D Coit, M Pulitzer, J Bini, R
Arora, NC Hanson, JA Tassello, D Frosina, P Moore, Y Chang. Am J Surg
Pathol 2009 Sep;33(9):1378-1385. 15 of 17 (88%) frozen Merkel cell
carcinoma samples were positive for MCV by PCR. "A tissue microarray of
36 MCCs, 7 combined squamous and neuroendocrine carcinomas of the skin,
and 26 pulmonary neuroendocrine carcinomas were also examined by IHC.
Of the 36 MCCs assembled on a microarray, 32 (89%) tumors expressed
CK20, and 27 (75%) were immunoreactive with CM2B4. The skin tumors with
a combined squamous and neuroendocrine phenotype and all pulmonary
neuroendocrine carcinomas failed to react with CM2B4."
Human Merkel cell polyomavirus infection II. MCV is a common human
infection that can be detected by conformational capsid epitope
immunoassays. YL Tolstov, DV Pastrana, H Feng, JC Becker, FJ Jenkins, S
Moschos, Y Chang, CB Buck, PS Moore. Int J Cancer 2009 Sep
15;125(6):1250-1256. "Among MCC patients, all 21 (100%) patients tested
with MCV-positive tumors had high serum MCV IgG but not high MCV IgM
levels. Only 3 of 6 (50%) MCC patients with MCV-negative tumors were
positive for MCV antibodies. Sera from most adults, including 107 of
166 (64%) blood donors, 63 of 100 (63%) commercial donors and 37 of 50
(74%) systemic lupus erythematosus patients, show evidence for prior
MCV exposure.... Although past exposure to MCV is common among all
adult groups, MCC patients have a markedly elevated MCV IgG response
compared with control patients."
Human Merkel cell polyomavirus infection II. MCV is a common human
infection that can be detected by conformational capsid epitope
immunoassays. YL Tolstov, DV Pastrana, H Feng, JC Becker, FJ Jenkins, S
Moschos, Y Chang, CB Buck, PS Moore. Int J Cancer 2009 Sep
15;125(6):1250-1256. "Among MCC patients, all 21 (100%) patients tested
with MCV-positive tumors had high serum MCV IgG but not high MCV IgM
levels. Only 3 of 6 (50%) MCC patients with MCV-negative tumors were
positive for MCV antibodies. Sera from most adults, including 107 of
166 (64%) blood donors, 63 of 100 (63%) commercial donors and 37 of 50
(74%) systemic lupus erythematosus patients, show evidence for prior
MCV exposure. Age-specific MCV prevalence was determined by examining a
cross-sectional distribution of 150 Langerhans cell histiocytosis (an
unrelated neoplasm) patient sera. MCV prevalence increases from 50%
among children age 15 years or younger to 80% among persons older than
50 years. We did not find evidence for vertical transmission among
infants."
Detection of Merkel cell polyomavirus in Merkel cell carcinoma and
Kaposi's sarcoma. H Katano, H Ito, Y Suzuki, T Nakamura, Y Sato, T
Tsuji, K Matsuo, H Nakagawa, T Sata. J Med Virol 2009 Sep
22;81(11):1951-1958. MCPyV-DNA was detected in 6 of 11 (55%) cases of
Merkel cell carcinoma by nested PCR and real-time PCR. MCPyV-positive
cases had different histology from MCPyV-negative cases.
Detection of Merkel cell polyomavirus DNA in Merkel cell carcinomas.
E Varga, M Kiss, K Szabó, L Kemény. Br J Dermatol 2009
Oct;161(4):930-2. "Nine primary or recurrent MCCs from
seven patients were examined; 29 other tumours (squamous cell, basal
cell and basosquamous carcinomas and malignant melanomas) were examined
for comparative purposes.... The presence of viral T antigen and/or
viral capsid DNA sequences was demonstrated in seven of the eight MCC
lesions. None of the comparative samples contained MCV DNA."
Frequent occurrence of RASSF1A promoter hypermethylation and merkel
cell polyomavirus in merkel cell carcinoma. P Helmbold, C Lahtz, A Enk,
P Herrmann-Trost, WC Marsch, H Kutzner, RH Dammann. Mol Carcinog 2009
Oct;48(10):903-9. "MCPyV was found in 90 of 98 (92%) MCC,
however, no SV40 signal was detected. No correlation between TSG
hypermethylation and viral infection was found."
Merkel cell polyomavirus in cutaneous squamous cell carcinoma of
immunocompetent individuals. AM Dworkin, SY Tseng, DC Allain, OH
Iwenofu, SB Peters, AE Toland. J Invest Dermatol 2009
Dec;129(12):2868-74. "We detected MCPyV in 15% (26/177) of SCC DNA
samples
and 17% (11/63) of adjacent skin DNA samples from 21 of 58 (36%)
individuals studied.... All sequenced SCC samples had a common mutation
truncating the LT antigen that provides indirect evidence of viral
integration."
Merkel cell polyomavirus DNA detection in lesional and nonlesional
skin from patients with Merkel cell carcinoma or other skin diseases. V
Foulongne, O Dereure, N Kluger, JP Molès, B Guillot, M Segondy.
Br J Dermatol 2010 Jan;162(1):59-63. "MCPyV DNA was detected in 14 of
18 (78%) patients with MCC, five of 18 (28%) patients with other skin
diseases (P = 0.007) and one of six (17%) clinically healthy subjects.
In patients with MCC, viral DNA was detected in nine of 11 (82%)
tumours and in 10 of 14 (71%) nontumoral skin samples (P = 0.66). MCPyV
DNA levels were higher in MCC tumours than in nontumoral skin from
patients with MCC, and than in lesional or nonlesional skin from
patients with other cutaneous disorders. Signature mutations in the T
antigen gene were not identified in the two MCC tumour specimens
analysed."
Prevalence of MCPyV in Merkel cell carcinoma and non-MCC tumors. C
Andres, B Belloni, U Puchta, CA Sander, MJ Flaig. J Cutan Pathol 2010
Jan;37(1):28-34. 33 MCC samples and 33 age- and
sex-matched samples of sun exposed non-MCC tumors (12 seborrheic
keratoses, 11 basal cell carcinomas, and 10 lentigo maligna melanomas).
"MCPyV sequences were detected in 21 MCC samples (64%) and in 2 non-MCC
tumors of sun exposed skin (6%; both SK-patients). Neither the tissue
samples from BCC nor LMM proved positive for MCPyV sequences."
Prevalence of Merkel cell polyomavirus among Swiss Merkel cell
carcinoma patients. J Mangana, P Dziunycz, K Kerl, R Dummer, A Cozzio.
Dermatology 2010;221(2):184-188. "We detected viral DNA in 20 out of 30
cases of MCC and in 0 out of 19 control samples."
Merkel cell carcinoma subgroups by Merkel cell polyomavirus DNA
relative abundance and oncogene expression. K Bhatia, JJ Goedert, R
Modali, L Preiss, LW Ayers. Int J Cancer 2010 May 1;126(9):2240-2246.
"MCPyV was detected in 19 of 23 (74%) primary MCC tumors, but 8 of
these had less than 1 viral copy per 300 cells. Viral abundance of
0.06-1.2 viral copies/cell was directly related to presence of
retinoblastoma gene product (pRb) and terminal deoxyribonucleotidyl
transferase (TdT) by immunohistochemical staining (p </= 0.003).
Higher viral abundance tumors tended to be associated with less p53
expression, younger age at diagnosis and longer survival (p </=
0.08)."
Distinct Merkel Cell Polyomavirus Molecular Features in Tumour and
Non Tumour Specimens from Patients with Merkel Cell Carcinoma. HC
Laude, B Jonchère, E Maubec, A Carlotti, E Marinho, B Couturaud,
M
Peter, X Sastre-Garau, M-F Avril, N Dupin, F Rozenberg. PLoS Pathog
2010 Aug. 31 / 33 tumors were positive for markers of MPyV. "Patients
with MCC containing more than 1 viral genome copy per cell had a longer
period in complete remission than patients with less than 1 copy per
cell (34 vs 10 months, P = 0.037)" "However, in two models of
adenovirus and polyomavirus-induced oncogenesis, the dependence of
transformed cells on viral oncoproteins was reversed upon time, since
cells conserved an oncogenic phenotype while viral expression was
shut-down in one case and viral sequences were lost in the other. These
findings suggest that transformed cells acquire subsequent genetic
alterations which circumvent their need for a continued expression of
viral oncoproteins. Therefore, more cellular genetic
alterations may be necessary in virus-unrelated than in virus-related
oncogenesis."
Lack of evidence for basal or squamous cell carcinoma infection with
Merkel cell polyomavirus in immunocompetent patients with Merkel cell
carcinoma. DM Reisinger, JD Shiffer, AB Cognetta Jr, Y Chang, PS Moore.
J Am Acad Dermatol 2010 Sep;63(3):400-403. "MCV T antigen was readily
detected in 15 (75%) of 20 MCC tumors including 11 MCC tumors from
patients with secondary SCC or BCC. In contrast to MCC, none of these
secondary BCC or SCC was MCV T-antigen positive.
Antibodies to Merkel Cell Polyomavirus T Antigen Oncoproteins
Reflect Tumor Burden in Merkel Cell Carcinoma Patients. KG Paulson, JJ
Carter LG Johnson, KW Cahill, JG Iyer, D Schrama, JC Becker, MM
Madeleine, P Nghiem, Galloway. Cancer Res 2010 Nov 1;70(21):8388-97.
"Among 530 population control subjects, these antibodies were
present in only 0.9% and were of low titer. In contrast, among 205 MCC
cases, 40.5% had serum IgG antibodies that recognize a portion of T-Ag
shared between small and large T-Ags. Among cases, titers of T-Ag
antibodies fell rapidly (∼8-fold per year) in patients whose cancer did
not recur, whereas they rose rapidly in those with progressive disease.
Importantly, in several patients who developed metastases, the rise in
T-Ag titer preceded clinical detection of disease spread."
The new polyomavirus (MCPyV) does not affect the clinical course in
MCCs. J Handschel, D Müller, RA Depprich, MA Ommerborn, NR
Kübler, C Naujoks, J Reifenberger, KL Schäfer, S Braunstein.
Int J Oral Maxillofac Surg 2010 Nov;39(11):1086-1090. "59 samples from
44 patients were analysed for the presence of MCPyV using the primers
LT3, VP1 and LT1.... 58% of specimens were positive for MCPyV. Of
these, LT3 was positive in 53%, VP1 in 37% and LT1 in 10%."
Merkel cell carcinoma: Our experience with seven patients in Korea
and a literature review. KJ Woo, YL Choi, HS Jung, G Jung, YK Shin, KT
Jang, J Han, JK Pyon. J Plast Reconstr Aesthet Surg 2010
Dec;63(12):2064-70. All seven patients were positive for Merkel cell
polyomavirus.
Homo- and heterotypic cell-cell contacts in Merkel cells and Merkel
cell carcinomas: heterogeneity and indications for cadherin switching.
AM Werling, Y Doerflinger, JM Brandner, F Fuchs, JC Becker, D Schrama,
H Kurzen, S Goerdt, WK Peitsch. Histopathology 2011 Jan;58(2):286-303.
84% of 52 MCCs were positive for MCV DNA.
Presence of Merkel cell polyomavirus in Japanese cutaneous squamous
cell carcinoma. M Murakami, M Imajoh, T Ikawa, H Nakajima, M Kamioka, Y
Nemoto, T Ujihara, J Uchiyama, S Matsuzaki, S Sano, M Daibata. J Clin
Virol 2011 Jan;50(1):37-41. 30 squamous cell carcinomas
and 10 basal cell carcinomas in Japanese. Viral sequences of the LT3
gene were found in 4 of 30 (13%) of SCCs. BCCs were all negative for
MCPyV.
Merkel cell polyomavirus in Merkel cell carcinoma of Italian
patients. F Paolini, P Donati, A Amantea, S Bucher, E Migliano, A
Venuti. Virol J 2011 Mar 7;8:103. "The presence of viral T antigen
and/or viral capsid DNA sequences was demonstrated in eight of the nine
MCC lesions, whereas RNA transcripts were detected in three MCCs."
Association of Merkel cell polyomavirus infection with morphologic
differences in Merkel cell carcinoma. S Kuwamoto, H Higaki, K Kanai, T
Iwasaki, H Sano, K Nagata, K Kato, M Kato, I Murakami, Y Horie, O
Yamamoto, K Hayashi. Hum Pathol 2011 May;42(5):632-640. "Merkel cell
polyomavirus was detected in 20 (77%) of 26 Merkel cell carcinoma
cases, including 4 Merkel cell carcinomas combined with squamous cell
carcinomas. Interestingly, Merkel cell polyomavirus was detected only
in ordinary (pure) Merkel cell carcinomas; none of the 4 combined
Merkel cell carcinomas + squamous cell carcinomas was positive for
Merkel cell polyomavirus (P = .001). Morphometric analyses revealed
that Merkel cell polyomavirus-negative Merkel cell carcinomas had more
irregular nuclei (P < .001) and more abundant cytoplasm (P = .001)
than Merkel cell polyomavirus-positive Merkel cell carcinomas, which
had uniform round nuclei and scant cytoplasm."
Expression of p63 is the sole independent marker of aggressiveness
in localised (stage I-II) Merkel cell carcinomas. S Asioli, A Righi, D
de Biase, L Morandi, V Caliendo, F Picciotto, G Macripò, F
Maletta, LV di Cantogno, L Chiusa, V Eusebi, G Bussolati. Mod Pathol
2011 Jul 15 [Epub ahead of print]. "Presence of Merkel cell
polyomavirus DNA sequences was detected in 86% (60/70) of Merkel cell
carcinomas and did not emerge as a significant prognostic parameter."
Association of Merkel cell polyomavirus infection with tumor p53,
KIT, stem cell factor, PDGFR-alpha and survival in Merkel cell
carcinoma. M Waltari, H Sihto, H Kukko, V Koljonen, R Sankila, T
Böhling, H Joensuu. Int J Cancer 2011 Aug 1;129(3):619-628.
"Most (77.0%) of the 87 tumors contained MCPyV DNA and 37 (42.5%)
expressed KIT, whereas PDGFRα, p53, SCF and pKIT expression was less
common (31.9%, 22.8%, 8.6% and 4.8%, respectively)."
Merkel cell polyomavirus status is not associated with clinical
course of merkel cell carcinoma. D Schrama, WK Peitsch, M Zapatka, H
Kneitz, R Houben, S Eib, S Haferkamp, PS Moore, M Shuda, JF Thompson, U
Trefzer, C Pföhler, RA Scolyer, JC Becker. J Invest Dermatol 2011
Aug;131(8):1631-1638. 86% of 174 MCC patients from Australia and Germany
were positive for MCC, with no significant difference in prevalence
between the countries.
A specific signature of Merkel cell polyomavirus persistence in
human cancer cells. H zur Hausen. Proc Natl Acad Sci USA. 2008 Oct
21;105(42):16063-16064. Mutations in the helicase part of the large T
antigen of MCpyV result in replication incompetence. These types of
mutation in other polyomaviruses have been shown to increase their
transformation potential.
T antigen mutations are a human tumor-specific signature for Merkel
cell polyomavirus. M Shuda, H Feng, HJ Kwun, ST Rosen, O Gjoerup, PS
Moore, Y Chang. Proc Natl Acad Sci USA 2008 Oct 21;105(42):16272-16277.
"Nine MCC tumor-derived LT genomic sequences have been examined, and
all were found to harbor mutations prematurely truncating the MCV LT
helicase. In contrast, four presumed episomal viruses from nontumor
sources did not possess this T antigen signature mutation." The
mutations "do not affect retinoblastoma tumor suppressor protein (Rb)
binding by LT but do eliminate viral DNA replication capacity." "Only
WT LT expression activates replication of integrated MCV DNA in MKL-1
cells. Our findings suggest that MCV-positive MCC tumor cells undergo
selection for LT mutations to prevent autoactivation of integrated
virus replication that would be detrimental to cell survival. Because
these mutations render the virus replication-incompetent, MCV is not a
"passenger virus" that secondarily infects MCC tumors."
The prostate cancer-associated human retrovirus XMRV lacks direct
transforming activity but can induce low rates of transformation in
cultured cells. MJ Metzger, CJ Holguin, R Mendoza, AD Miller. J Virol
2010 Feb;84(4):1874-1880. "Here we have used cultured fibroblast and
epithelial cell lines to test the hypothesis that XMRV might have
direct transforming activity but found only rare transformation events
suggestive of indirect transformation, even when the target cells
expressed the human Xpr1 cell-entry receptor for XMRV."
Merkel cell polyomavirus infected Merkel cell carcinoma cells
require expression of viral T antigens. R Houben, M Shuda, R Weinkam, D
Schrama, H Feng, Y Chang, PS Moore, JC Becker. J Virol 2010
Jul;84(14):7064-7072. "We knocked down MCV T antigen (TA) expression in
MCV-positive MCC cell lines using three different shRNA-expressing
vectors targeting exon 1 of the TAs... Notably, all MCV-positive MCC
cell lines underwent growth arrest and/or cell death upon TA knock
down, whereas proliferation of MCV-negative cell lines remained
unaffected... Our study provides the first direct experimental evidence
for TA expression being necessary for maintenance of MCV-positive MCC
and thereby identifies the TAs as possible targets for future
therapies."
Merkel cell polyomavirus small T antigen mRNA level is increased
following in vivo UV-radiation. A Mogha, A Fautrel, N Mouchet, N Guo, S
Corre, H Adamski, E Watier, L Misery, MD Galibert. PLoS One 2010 Jul
2;5(7):e11423. "Two patients were infected with two new variants of
MCPyV, present in their episomal form and RT-QPCR analyses on
SSR-irradiated skin samples showed a specific and unique dose-dependent
increase of MCPyV small t antigen transcript. A luciferase based in
vitro assay confirmed that small t promoter is indeed UV-inducible."
Seroepidemiology of Human Polyomaviruses. JM Kean, S Rao, M Wang, RL
Garcea. PLoS Pathogens 2009 Mar;5(3). Seroprevalence in 1501 healthy
adult blood donors was SV40 (9%), BKV (82%), JCV (39%), LPV (15%), KIV
(55%), WUV (69%), MCV strain 350 (25%), and MCV strain 339 (42%).
Seroprevalence in 721 pediatric patients (<21 y) was similar.
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