ライフサイエンスコーパス: MCPyV

1 MCPyV DNA was present in 13 of 18 samples, and HPV, HPyV

2 MCPyV has been difficult to propagate in vitro.

3 MCPyV infection and transformation of pro-/pre-B cells a

4 MCPyV infection is highly prevalent in adults, with age

5 MCPyV infection showed the highest prevalence (65.1% of

6 MCPyV is associated with a highly aggressive form of ski

7 MCPyV is the first polyomavirus to be clearly associated

8 MCPyV isolated from MCC typically contains wild-type ST

9 MCPyV large T antigen could bind to Rb but was unable to

10 MCPyV small T (sT) antigen has emerged as the key oncoge

11 MCPyV sT translocates to nuclear foci containing activel

12 MCPyV sT, when coexpressed with ATOH1, is thus sufficien

13 MCPyV-negative tumors also displayed high overall mutati

14 MCPyV-negative tumors showed decreased RB1 expression, w

15 when a replication-defective LT mutant or an MCPyV-origin mutant was introduced in place of wild-type

16 tochemistry with two distinct antibodies and MCPyV DNA using quantitative PCR.

17 tween the host DNA damage response (DDR) and MCPyV replication.

18 ecause these tumors often express PD-L1, and MCPyV-specific T cells express PD-1.

19 ntially expressed between MCPyV-negative and MCPyV-positive MCCs, with significant differential expre

20 tatus was concordant for all tumor pairs and MCPyV positive tumors harbored predominatly subclonal mu

21 analysis showed that these DDR proteins and MCPyV LT in fact colocalized at the actively replicating

22 understand why approximately 20% of MCCs are MCPyV-negative.

23 e sets were differentially expressed between MCPyV-negative and MCPyV-positive MCCs, with significant

24 have investigated any potential link between MCPyV T antigen expression and the highly metastatic nat

25 imilar to native MCPyV infection, where both MCPyV origin and LT are present, the host DDR machinery

26 approximately 20% of MCCs are not driven by MCPyV and that such virus-negative MCCs, which can be qu

27 the skin cell type productively infected by MCPyV remains a central question.

28 Tumors were called MCPyV-positive if two or more of these three assays indi

29 ercentage of Australian MCC cases containing MCPyV may be lower than that of North American cases.

30 ib as an effective inhibitor for controlling MCPyV infection.

31 cidofovir as a possible drug for controlling MCPyV infection.

32 sT is a potential drug target for dampening MCPyV infection.

33 We did not detect MCPyV in any matched normal blood DNA (0/57), but observ

34 rt that a novel monoclonal antibody detected MCPyV large T antigen expression in 56 of 58 (97%) uniqu

35 We detected MCPyV in 15% (26/177) of SCC DNA samples and 17% (11/63)

36 To address these controversies, we detected MCPyV large T antigen using immunohistochemistry with tw

37 h similar mechanisms of pathogenesis, either MCPyV-mediated or ultraviolet light-mediated.

38 to occur in MCC tumors that fail to express MCPyV large T antigen.

39 Mice expressing MCPyV T antigens developed hyperplasia, hyperkeratosis,

40 hat these host DDR factors are important for MCPyV DNA replication, providing new insight into the ho

41 his, we established a cell culture model for MCPyV infection, which will facilitate investigation of

42 cation of a potential host cell receptor for MCPyV will aid in the elucidation of its entry mechanism

43 e identify a putative host cell receptor for MCPyV.

44 ire of quantitative PCR primers specific for MCPyV to improve the detection of viral DNA in MCC.

45 Epidemiological surveys for MCPyV seropositivity and sequencing analyses of healthy

46 Furthermore, MCPyV-truncated large T antigen was more effective than

47 In this report, we identify MCPyV sT as a novel Fe/S cluster protein and show that c

48 and ATR-mediated DDR pathways accumulate in MCPyV large T antigen (LT)-positive nuclear foci in cell

49 and ATR-mediated DDR pathways accumulate in MCPyV LT-positive nuclear foci.

50 The discovery of Fe/S clusters in MCPyV sT opens new avenues to the study of the structure

51 ns of Fe/S cluster-coordinating cysteines in MCPyV sT abolish its ability to stimulate viral replicat

52 ration of decreased RB protein expression in MCPyV-negative tumors and increased peritumoral CD8+ T l

53 utations in PRUNE2 and NOTCH family genes in MCPyV-negative MCC.

54 In contrast, mutation burden was low in MCPyV-positive tumors (0.40 +/- 0.09 mutations/Mb) and l

55 r, the mechanisms underlying pathogenesis in MCPyV-negative MCCs remain poorly understood.

56 e microtubule-associated protein stathmin in MCPyV ST-mediated microtubule destabilization and cell m

57 encoded by several polyomaviruses including MCPyV, but also provides insight into de novo protein ev

58 ases of MCC reported to date, the integrated MCPyV genome has undergone mutations in the large T anti

59 pment of Merkel cell carcinoma (MCC), making MCPyV the first polyomavirus to be clearly associated wi

60 Similar to native MCPyV infection, where both MCPyV origin and LT are pres

61 we show that, in cells infected with native MCPyV virions, components of the ATM- and ATR-mediated D

62 e nuclear foci in cells infected with native MCPyV virions.

63 ormed integrative sequencing on two cases of MCPyV-negative MCC, as well as a validation cohort of 14

64 irst report demonstrating the coexistence of MCPyV and HPV-17 in cutaneous SCC.

65 Coexpression of MCPyV tLT did not appreciably alter the phenotype driven

66 y polymerase chain reaction for detection of MCPyV and epidermodysplasia verruciformis HPV (EV-HPV) t

67 to increase the sensitivity of detection of MCPyV in MCC by developing antibodies capable of detecti

68 stly inhibits the sT-mediated enhancement of MCPyV replication but has little effect on the basal vir

69 competent individuals warrants evaluation of MCPyV as an etiologic agent in the carcinogenesis of SCC

70 Our data establish that expression of MCPyV sTAg alone is sufficient for rapid neoplastic tran

71 recombinase expression induced expression of MCPyV T antigens in stratified squamous epithelial cells

72 We tested 21 MCCs for the expression of MCPyV, TdT, PAX5, IgG, IgM, IgA, kappa, and lambda by im

73 ted, and alternatively spliced 57kT forms of MCPyV large T antigen.

74 nst the large T (LT) antigen and VP1 gene of MCPyV.

75 The importance of MCPyV sT led us to investigate sT functions and to ident

76 antigens, but the molecular pathogenesis of MCPyV-negative MCC is largely unexplored.

77 te genes contributing to the pathogenesis of MCPyV-negative MCCs, we performed DNA microarray analysi

78 n reaction products revealed the presence of MCPyV and HPV-17 DNA.

79 ood DNA (0/57), but observed the presence of MCPyV DNA in 1 of 12 normal mouthwash DNAs.

80 The presence of MCPyV in approximately 15% of SCCs from immunocompetent

81 To test for the presence of MCPyV in immunocompetent SCC patients, we used PCR prime

82 With the high prevalence of MCPyV infection and the increasing amount of MCC diagnos

83 e associated with an increased prevalence of MCPyV infection in eyebrow hair and normal skin swab spe

84 imply that the deletion of the C terminus of MCPyV large T antigen found in MCC serves not only to di

85 ve an important role in the tumorigenesis of MCPyV-negative MCCs.

86 hat we call Merkel cell polyomavirus (MCV or MCPyV).

87 irst case in which Merkel cell polyomavirus (MCPyV) and human papillomavirus subtype 17 (HPV-17) were

88 ) that contain the Merkel cell polyomavirus (MCPyV) and the clinical significance of tumor viral stat

89 Infection with Merkel cell polyomavirus (MCPyV) can lead to Merkel cell carcinoma (MCC), a lethal

90 Merkel cell polyomavirus (MCPyV) causes the majority of cases of Merkel cell carci

91 Merkel cell polyomavirus (MCPyV) causes the majority of MCC cases due to the expre

92 frequently contain Merkel cell polyomavirus (MCPyV) DNA and express viral transforming antigens, sT a

93 st 80% of all MCC, Merkel cell polyomavirus (MCPyV) DNA has undergone clonal integration into the hos

94 Merkel cell polyomavirus (MCPyV) expressing viral T antigens is a common feature o

95 The Merkel cell polyomavirus (MCPyV) genome undergoes clonal integration into the host

96 dicates a role for Merkel cell polyomavirus (MCPyV) in the development of Merkel cell carcinoma (MCC)

97 Merkel cell polyomavirus (MCPyV) is a common infectious agent that is likely invol

98 Merkel cell polyomavirus (MCPyV) is frequently associated with Merkel cell carcino

99 ominine hosts, the Merkel cell polyomavirus (MCPyV) lineage.

100 Merkel cell polyomavirus (MCPyV) may contribute to tumorigenesis in a subset of tu

101 Merkel cell polyomavirus (MCPyV) plays an important role in Merkel cell carcinoma

102 r alterations, and Merkel cell polyomavirus (MCPyV) sequence were analyzed and compared between clini

103 The Merkel cell polyomavirus (MCPyV) was identified recently in human Merkel cell carc

104 of a polyomavirus, Merkel cell polyomavirus (MCPyV), and MCC tumor cells express putative polyomaviru

105 The Merkel cell polyomavirus (MCPyV), discovered in 2008, drives the development of mo

106 Merkel cell polyomavirus (MCPyV), identified in the majority of MCCs, may drive tu

107 he early region of Merkel cell polyomavirus (MCPyV), the causative agent of most Merkel cell carcinom

108 bed polyoma virus, Merkel cell polyomavirus (MCPyV), was found in Merkel cell carcinoma (MCC), a rare

109 olet light and the Merkel-cell polyomavirus (MCPyV).

110 decade, including Merkel cell polyomavirus (MCPyV).

111 DNA from a new polyomavirus, MCPyV, was recently shown to be clonally integrated in s

112 alence, and persistence of 9 polyomaviruses (MCPyV, BK polyomavirus, KI polyomavirus, JC polyomavirus

113 ntibodies to the viral capsid indicate prior MCPyV infection, they provide limited clinical insight i

114 s natural host cells that support productive MCPyV infection.

115 human dermal fibroblasts support productive MCPyV infection.

116 It has also been shown to promote MCPyV LT-mediated replication by stabilizing LT.

117 investigated whether antibodies recognizing MCPyV large and small tumor-associated antigens (T-Ag) w

118 We found that recombinant MCPyV VP1 pentameric capsomeres both hemagglutinated she

119 sly established system, in which recombinant MCPyV episomal DNA is autonomously replicated in culture

120 ll interfering RNA (siRNA) knockdown reduced MCPyV DNA replication without significantly affecting LT

121 fact colocalized at the actively replicating MCPyV replication complexes, which were absent when a re

122 Verhaegen et al. report MCPyV small T-antigen-expressing transgenic mice that no

123 roteins are important for maintaining robust MCPyV DNA replication.

124 Moreover, we show that sT sensitizes MCPyV replication to cidofovir inhibition.

125 pathway and other growth factors stimulates MCPyV infection.

126 To further study MCPyV replication, we employed our previously establishe

127 d peritumoral CD8+ T lymphocytes surrounding MCPyV-positive tumors.

128 aracterized by tumor sequencing and targeted MCPyV sequencing to distinguish independent primary tumo

129 n this issue, Becker et al. demonstrate that MCPyV DNA can be isolated from 85% of primary European M

130 Intriguingly, we demonstrate that MCPyV ST expression promotes microtubule destabilization

131 Indeed, we demonstrated that MCPyV sT enhances LT-mediated replication in a manner th

132 We discovered that MCPyV sT purified from bacteria contains iron-sulfur (Fe

133 Regardless of clonality, we found that MCPyV status was concordant for all tumor pairs and MCPy

134 n, our results suggested the hypothesis that MCPyV sT might be directly involved in viral replication

135 We hypothesized that MCPyV would be present in SCCs.

136 These results indicate that MCPyV is present in MCC tumors more frequently than prev

137 These results indicate that MCPyV T antigens are tumorigenic in vivo, consistent wit

138 This finding further indicates that MCPyV sT plays a direct role in stimulating viral DNA re

139 These reports support the possibility that MCPyV is etiologically involved in at least some cases o

140 ious studies have consistently reported that MCPyV can be detected in approximately 80% of all MCC tu

141 We further show that MCPyV ST induces this process by regulating the phosphor

142 quantitative proteomic approach to show that MCPyV ST promotes differential expression of cellular pr

143 paramagnetic resonance analysis showed that MCPyV sT coordinates a [2Fe-2S] and a [4Fe-4S] cluster.

144 analyses of healthy human skin suggest that MCPyV may represent a common component of the human skin

145 tween the analyzed gangliosides suggest that MCPyV VP1 likely interacts with sialic acids on both bra

146 The MCPyV status of MCCs was determined by PCR for viral DNA

147 f DDR factor/LT replication complexes at the MCPyV origin but also provides a platform for further st

148 ost cell genome, and most tumors express the MCPyV large and small T antigens.

149 However, the MCPyV life cycle and its oncogenic mechanism remain poor

150 mechanistic role of host DDR factors in the MCPyV life cycle and virus-associated oncogenesis.

151 ight into the host machinery involved in the MCPyV life cycle.

152 ng, but not required for, replication of the MCPyV genome.

153 ral genome with persistent expression of the MCPyV large T (LT) and small T (ST) antigen.

154 In contrast, expression of the MCPyV large T antigen C-terminal 100 residues could inhi

155 process at play during the evolution of the MCPyV lineage.

156 ty of MCC cases due to the expression of the MCPyV small and large tumor antigens (ST and LT, respect

157 Serum antibodies recognizing the MCPyV capsid protein VP1 are detectable at high titer in

158 We demonstrate that the MCPyV small tumor antigen (ST) promotes the destabilizat

159 molecular mechanisms have been attributed to MCPyV tumor antigen-mediated cellular transformation or

160 rming functions of full-length and truncated MCPyV large T antigen are unknown.

161 sociated with the Merkel cell polyoma virus (MCPyV).

162 reviously established system for visualizing MCPyV replication complexes in cells.

163 ors showed decreased RB1 expression, whereas MCPyV-positive tumors were enriched for immune response

164 in our knowledge remains the basis by which MCPyV, among all 12 human polyomaviruses, is the only on

165 avirus) and examined factors associated with MCPyV infection in a prospective cohort of 209 men initi

166 he response rate was 62% among patients with MCPyV-positive tumors (10 of 16 patients) and 44% among

167 polyomaviruses (BKPyV, JCPyV, KIPyV, WUPyV, MCPyV, HPyV6, HPyV7, TSPyV, HPyV9, HPyV10) and 5 herpesv