ライフサイエンスコーパス: reovirus

1 serotonin antagonist, enhanced infection by reovirus.

2 inosine-polycytidylic acid, influenza A, and reovirus.

3 esponses to poly I:C, influenza A virus, and reovirus.

4 s that bind the attachment protein sigma1 of reovirus.

5 nisms of antibody-mediated neutralization of reovirus.

6 cifically lacking IEC Ifnlr1 expression with reovirus.

7 in altering the cell attachment property of reovirus.

8 nction protein that serves as a receptor for reovirus.

9 igma1 of serotype 1 (T1) and serotype 3 (T3) reoviruses.

10 following infection of neonatal mice with T3 reoviruses.

11 Reovirus, a model system for studying the entry mechanis

12 capable of inhibiting cytotoxicity caused by reovirus, a prototype double-stranded RNA virus.

13 in humans supports a role for infection with reovirus, a seemingly innocuous virus, in triggering the

14 Reoviruses, a model system for entry of nonenveloped vir

15 Furthermore, reovirus administration in tumor-bearing hosts drives ti

16 The effect of adding reovirus after photodynamic therapy was also assessed.

17 The pathogenesis of reovirus, an unrelated enteric virus, also was more seve

18 e intestine, intestinal epithelial cells for reovirus and intestinal mononuclear phagocytes for MNV.

19 Reovirus and vesicular stomatitis virus single-cycle yie

20 rganization similar to that of homodimers of reoviruses and other dsRNA mycoviruses.

21 Reoviruses are double-stranded RNA viruses that infect h

22 Reoviruses are double-stranded RNA viruses that infect t

23 Reoviruses are important human, animal and plant pathoge

24 Mammalian orthoreoviruses (reoviruses) are nonenveloped double-stranded RNA viruses

25 Although we have shown that avian reovirus (ARV) p17-mediated inhibition of Akt leads to i

26 acilitate replication or production of avian reovirus (ARV); nevertheless, how ARV induces autophagy

27 ue will accelerate production of recombinant reoviruses as candidates to enhance therapeutic potency.

28 lines were less susceptible to infection by reovirus, as they exhibited significantly lower percenta

29 ntly associated with a novel Atlantic salmon reovirus (ASRV), is currently one of the most prevalent

30 to mu1C, a previously described hallmark of reovirus assembly.

31 How reovirus attaches to host cells has been extensively cha

32 We determined the structure of serotype 1 reovirus attachment protein sigma1 alone and in complex

33 Reovirus attachment protein sigma1 engages glycan recept

34 Reovirus attachment protein sigma1 is an elongated trime

35 aradigm, in this article we demonstrate that reovirus augments tumor-associated immunosuppression imm

36 rence in cytotoxicity observed between added reovirus before or after photodynamic therapy.

37 Expression of NgR1 confers reovirus binding and infection of nonsusceptible cells.

38 a suggest that sigma1 length is required for reovirus binding to cells.

39 We demonstrate that reovirus binds Nogo receptor NgR1, a leucine-rich repeat

40 Mammalian reovirus binds to cell surface glycans and junctional ad

41 Reovirus binds to cell surface glycans, junctional adhes

42 Baboon reovirus (BRV) is a member of the fusogenic subgroup of

43 e identify that infection of host cells with reovirus can result in necroptosis.

44 nerve transection, indicating that wild-type reovirus can spread to the brain by the blood.

45 highlight regions of mu1 that stabilize the reovirus capsid and demonstrate that an enhanced propens

46 ct a backbone model of the entire grass carp reovirus capsid and provide valuable functional insights

47 rrent limitations in recovery of replicating reoviruses carrying large fluorescent protein tags, rese

48 Reovirus cell entry is initiated by viral attachment to

49 e the efficiency with which the next step in reovirus cell entry, namely, ISVP-to-ISVP* conversion, o

50 Thus, reovirus cell tropism can be governed by interactions be

51 Thus, reovirus cell tropism may be determined at early and lat

52 y of the adaptive immune response to enhance reovirus clearance.

53 Reovirus colocalizes with Src during cell entry, and reo

54 The killing effects of reovirus combined with PpIX-mediated photodynamic therap

55 The cooperativity between a reovirus component and lipids reveals a distinct virus-h

56 a functional role for sialylated glycans as reovirus coreceptors in the CNS.

57 otype serotonin receptor agonist, diminished reovirus cytotoxicity.

58 ns and suggest that distinct portions of the reovirus delta domain influence different steps during e

59 e organization represent the most simplified reovirus described to date, and phylogenetic analysis su

60 The proteases that promote reovirus disassembly and cell entry in the respiratory t

61 strain type 3 Dearing (T3D) sigma3 enhances reovirus disassembly and confers resistance to protease

62 findings reveal a new region that regulates reovirus disassembly and how perturbing a metastable cap

63 The initiating event in reovirus disassembly is the cathepsin-mediated proteolyt

64 rus transit to late endosomes and a delay in reovirus disassembly.

65 To determine the role of IRF-3 in reovirus disease, we infected newborn IRF-3(+/+) and IRF

66 Mammalian reoviruses display serotype-specific patterns of tropism

67 The double-stranded RNA virus mammalian reovirus displays broad cell, tissue, and host tropism.

68 ns of endothelial and hematopoietic JAM-A to reovirus dissemination and pathogenesis, we generated st

69 xx is present in Fas-expressing cells during reovirus encephalitis, suggesting a role for Daxx in Fas

70 nd that activated Bak is bound to p53 during reovirus encephalitis.

71 vels are increased in infected brains during reovirus encephalitis.

72 Enteric viruses, including poliovirus and reovirus, encounter a vast microbial community in the ma

73 Cellular factors that mediate reovirus endocytosis are poorly defined.

74 Reovirus engages junctional adhesion molecule A (JAM-A)

75 how polymorphic differences in mu1 influence reovirus entry events, we generated recombinant viruses

76 We show that interactions between reovirus entry intermediates and lipid membranes devoid

77 t to determine whether IFITM3 also restricts reovirus entry.

78 uggesting that Src is required for efficient reovirus entry.

79 reased intestinal tissue titers and enhanced reovirus fecal shedding.

80 Reolysin, a proprietary formulation of reovirus for cancer therapy, stimulated selective viral

81 will also expedite production of recombinant reovirus for mechanistic insights into reovirus protein

82 The reovirus fusion-associated small transmembrane (FAST) pr

83 The reovirus fusion-associated small transmembrane proteins

84 ral factories, and there is no evidence that reovirus genomic or messenger RNAs are spliced, suggesti

85 Ten isolates of a novel reovirus (genus Dinovernavirus) were detected by culturi

86 ur studies suggest that Bax is important for reovirus growth and pathogenesis in neurons and that the

87 Reovirus has been used to dissect mechanisms of viral pa

88 Oncolytic virotherapy with reovirus has demonstrated anti-cancer activity and minim

89 , however, many oncolytic viruses, including reovirus, have been reported to overturn such immunosupp

90 beling study of internalization of oncolytic reovirus in human dendritic cells, in a cryo-electron mi

91 rk of encephalitis and myocarditis caused by reovirus in newborn mice.

92 he first evidence of recovery of replicating reoviruses in which VFs can be labeled in live cells via

93 To understand how reovirus inclusions differ in productively and abortivel

94 ion is limited to brain regions that undergo reovirus-induced apoptosis and occurs in the cytoplasm a

95 erferon regulatory factor 3 (IRF-3) enhances reovirus-induced apoptosis following activation via reti

96 Finally, we found that reovirus-induced apoptosis occurred in Bax(-/-)Bak(-/-)

97 ed in Bax(-/-)Bak(-/-) MEFs, indicating that reovirus-induced apoptosis occurs independently of the p

98 611 of mu1 are necessary and sufficient for reovirus-induced apoptosis, and residues 594 and 595 ind

99 ese data imply a regulatory role for Daxx in reovirus-induced apoptosis, depending on its location in

100 fibroblasts where NF-kappaB is required for reovirus-induced apoptosis, the mu2 ITAM is advantageous

101 o determine whether IFN-beta is required for reovirus-induced apoptosis, we used type I IFN receptor-

102 ion and NOXA induction as novel mediators of reovirus-induced apoptosis.

103 elix 3 (residues 644 to 675), play a role in reovirus-induced apoptosis.

104 id protein mu1 is the primary determinant of reovirus-induced apoptosis.

105 y regulate the efficiency of viral entry and reovirus-induced cell apoptosis, respectively.

106 mitochondrial localization of p53 regulates reovirus-induced pathogenesis in the central nervous sys

107 we define genetic determinants that regulate reovirus-induced pathology following intranasal inoculat

108 Additionally, mu1- or reovirus-induced release of cytochrome c occurred effici

109 Reovirus induces myocarditis in neonatal mice, providing

110 Our data show that reovirus induces preferential differentiation of highly

111 pression of IFN-beta signaling and modulates reovirus induction of IFN-beta in cardiac myocytes.

112 also significantly upregulated in the SC of reovirus-infected animals compared to mock-infected cont

113 In addition, survival is enhanced in reovirus-infected Bak(-/-) mice compared to controls, de

114 , we demonstrate that Daxx is upregulated in reovirus-infected brain tissue through a type I interfer

115 Increased levels of p53 in reovirus-infected brains are not associated with increas

116 ay a role in neuronal apoptosis occurring in reovirus-infected brains.

117 downstream signaling, inhibits apoptosis of reovirus-infected cells.

118 gnaling are dispensable for the apoptosis of reovirus-infected cells.

119 and the efficient induction of apoptosis in reovirus-infected cells.

120 es apoptosis by eliciting Noxa expression in reovirus-infected cells.

121 nflammatory mediators were still produced in reovirus-infected INFAR(-/-) mice, demonstrating that IF

122 Interestingly, MNV- and reovirus-infected mice depleted of M cells showed reduce

123 y, apoptosis, and viral growth in the CNS of reovirus-infected mice.

124 This increase occurs in the cytoplasm of reovirus-infected neurons and is associated with the act

125 tochrome c and Smac release occurred in some reovirus-infected neurons in the absence of Bax; however

126 xtrinsic apoptotic signaling is activated in reovirus-infected neurons in vitro and in vivo, but the

127 Treatment of reovirus-infected primary mouse cortical neurons with a

128 that p53 is activated in the brain following reovirus infection and may provide a therapeutic target

129 Importantly, the combination of reovirus infection and proteasomal inhibition significan

130 or flexibility of sigma1 resulted in delayed reovirus infection and reduced viral titers.

131 und that 5-nonyloxytryptamine (5-NT) impairs reovirus infection by altering viral transport during ce

132 Furthermore, reovirus infection can be used as a promising approach t

133 Reovirus infection elicits production of type I interfer

134 induced at late times (36 to 48 h) following reovirus infection in a manner dependent on IRF-3 and NF

135 nse to 5'pp-RNA is essential for controlling reovirus infection in cultured cells and in mice.

136 atory and inflammatory proteases can promote reovirus infection in vitro and that preexisting inflamm

137 colocalizes with Src during cell entry, and reovirus infection induces phosphorylation of Src at the

138 Reovirus infection is a well-characterized experimental

139 Concordantly, reovirus infection is ablated in primary cortical neuron

140 dicate that the apoptotic response following reovirus infection is mediated directly by genes respons

141 the formation of p53/Bak complexes following reovirus infection of ex vivo brain slice cultures and r

142 itecture of sigma1 is required for efficient reovirus infection of host cells.

143 Further, reovirus infection of mice deficient in the expression o

144 Reovirus infection of the mouse SC was also associated w

145 Reovirus infection of the murine spinal cord (SC) was us

146 Despite differences in cell tropism, reovirus infection was also reduced in M cell-depleted m

147 Similar to reovirus infection, ectopic expression of mu1 caused rel

148 s infection in vivo Upon murine norovirus or reovirus infection, Ifnlr1 depletion in IECs largely rec

149 olecule screen to identify host mediators of reovirus infection, we found that treatment of cells wit

150 ength and flexibility at different stages of reovirus infection, we generated viruses with mutant sig

151 5-NT also blocked reovirus infection.

152 cells or primary cortical neurons abrogates reovirus infection.

153 for Daxx in Fas-mediated apoptosis following reovirus infection.

154 indicating that endogenous IFITM3 restricts reovirus infection.

155 y prodeath function for this molecule during reovirus infection.

156 ion uncoating is an essential early event in reovirus infection.

157 these inflammatory mediators and ISG during reovirus infection.

158 nce and prevent tissue injury in response to reovirus infection.

159 of necroptosis also requires late stages of reovirus infection.

160 However, IFITM3 did not restrict entry of reovirus infectious subvirion particles (ISVPs), which d

161 ecific Src-family kinase inhibitor, diminish reovirus infectivity by blocking a cell entry step.

162 In contrast, reovirus infectivity was not altered in cells expressing

163 d Src expression by RNA interference reduces reovirus infectivity, suggesting that Src is required fo

164 ndosome biogenesis and maturation influenced reovirus infectivity.

165 In contrast to MNV, reovirus infects enterocytes in the intestine.

166 Our analysis defines reovirus interactions with two neutralizing antibodies,

167 r capsid play an active role in the entry of reovirus into host cells.

168 Reovirus is an avirulent pathogen that elicits protectiv

169 lowing attachment to cell surface receptors, reovirus is internalized by receptor-mediated endocytosi

170 Following receptor engagement, reovirus is internalized into cells by receptor-mediated

171 The level of apoptosis induced by reovirus is significantly diminished in cells lacking No

172 ways during cell entry, and they reveal that reovirus ISVPs can take advantage of caveolar endocytosi

173 We found that entry and infection by reovirus ISVPs was inhibited by dynasore, an inhibitor o

174 Early steps in the reovirus life cycle, attachment, entry, and disassembly,

175 Reoviruses, like many eukaryotic viruses, contain an inv

176 The reovirus M1 gene-encoded mu2 protein is a strain-specifi

177 Structural studies of the reovirus membrane penetration protein, mu1, predict that

178 tly increased cytotoxic effect compared with reovirus monotherapy and photodynamic therapy (p=0.042)

179 Reovirus monotherapy induced cell death in the two pancr

180 ent understanding of cell entry by mammalian reovirus (MRV) virions and infectious subvirion particle

181 The dsRNA genome of mammalian reovirus (MRV), like the dsDNA genomes of herpesviruses

182 repression of IFN-beta signaling mediated by reovirus mu2 amino acid 208 is a determinant of the IFN-

183 Studies of strain-specific differences in reovirus mucosal infection and systemic dissemination ha

184 Neurotropic viruses, including mammalian reovirus, must disseminate from an initial site of repli

185 Reovirus myelitis was associated with the pronounced act

186 ting that IFN signaling is protective during reovirus myelitis.

187 fine the function of carbohydrate binding in reovirus neuropathogenesis.

188 he infected host, which is required for full reovirus neurovirulence.

189 adar1(-/-) and adar2(-/-) cells, and neither reovirus nor VSV showed enhanced cytotoxicity in adar1(-

190 While all other turreted reoviruses of known structures have at least two copies

191 this is the first in-vitro study to combine reovirus oncolytic viral therapy with PpIX-mediated phot

192 cytomegalovirus, vesicular stomatitis virus, reovirus, or adenovirus.

193 had no effect on vesicular stomatitis virus, reovirus, or lymphocytic choriomeningitis virus replicat

194 The reovirus outer capsid is stabilized by mu1 intratrimer,

195 Proteins that form the reovirus outer capsid play an active role in the entry o

196 The reovirus outer capsid protein mu1 forms a lattice surrou

197 The reovirus outer capsid protein mu1 is responsible for cel

198 Recent studies have indicated that the reovirus outer capsid protein mu1 is the primary determi

199 unknown relationship between two nonadjacent reovirus outer capsid proteins, sigma1 and mu1.

200 activity and protease susceptibility of the reovirus outer capsid.

201 tif (PBM) in the cytosolic tail of reptilian reovirus p14 FAST protein functions as a novel tribasic

202 l number of proteins needed to form a viable reovirus particle.

203 After attachment to the cell surface, reovirus particles and JAM-A codistribute into each of t

204 Reovirus particles are covered with 200 mu1/sigma3 heter

205 nts that regulate the appropriate sorting of reovirus particles in the endocytic pathway for disassem

206 e, the sigma1 protein mediates attachment of reovirus particles to host cells via interaction with ce

207 In this study, we found that reovirus particles traffic through early, late, and recy

208 multiple approaches to determine if uncoated reovirus particles, called intermediate subviral particl

209 iously described role for mu1 in influencing reovirus pathogenesis.

210 to controls, demonstrating a role for Bak in reovirus pathogenesis.

211 at carbohydrate binding by sigma1 influences reovirus pathology in the CNS.

212 inant reovirus for mechanistic insights into reovirus protein function and structure.

213 We previously reported that the reovirus protein mu2 from strain T1L, but not strain T3D

214 oligodendrocyte glycoprotein (MOG) fused to reovirus protein sigma1 (MOG-psigma1), which activates T

215 identified ITAM sequences in three mammalian reovirus proteins: mu2, sigma2, and lambda2.

216 sigma1, and the effect of the antibodies on reovirus receptor engagement.

217 s BRAF and PI3K inhibitors, and the anti-RAS reovirus Reolysin(R).

218 Mammalian reoviruses replicate in a broad range of hosts, cells, a

219 Reovirus replicates in cytoplasmic viral factories, and

220 After peroral entry into mice, reovirus replicates within the gastrointestinal tract an

221 r Hsc70 within viral factories, the sites of reovirus replication and assembly in cells.

222 Moreover, depletion of SRSF2 enhanced reovirus replication and cytopathic effect, suggesting t

223 letion of this cell splicing factor enhances reovirus replication and cytopathic effect.

224 ese findings indicate that components of the reovirus replication complex are mediators of cell-selec

225 A critical checkpoint in the reovirus replication cycle resides within viral cytoplas

226 est that SA binding enhances the kinetics of reovirus replication in neural tissues and highlight a f

227 However, JAM-A is dispensable for reovirus replication in the CNS.

228 vide new insights into mechanisms underlying reovirus replication in the respiratory tract and system

229 Reovirus replication was also significantly reduced in I

230 Moreover, mu2 amino acid 208 determines reovirus replication, both in initially infected cardiac

231 Beyond providing mechanistic insight into reovirus replication, our findings also show that reovir

232 To address the role of mRNA capping during reovirus replication, we assessed the benefits of adding

233 Cell entry of reovirus requires a series of ordered steps, which inclu

234 Membrane penetration by reovirus requires successive formation of two cell entry

235 d to T7 RNA polymerase alone while enhancing reovirus rescue from the current reverse genetics system

236 NP868R-assisted reovirus rescue will also expedite production of recombi

237 ine fever virus NP868R capping enzyme during reovirus rescue.

238 rus replication, our findings also show that reovirus reverse genetics rescue is enhanced 100-fold by

239 shows promise as a cancer therapy, efficient reovirus reverse genetics rescue will accelerate product

240 rategy for engineering recombinant mammalian reoviruses (rMRVs) to express exogenous polypeptides.

241 We demonstrate here that some mammalian reoviruses, RNA viruses that replicate strictly in the c

242 new virions, we developed a new recombinant reovirus S1 gene that expressed the fluorescent protein

243 Encephalitis induced by reovirus serotype 3 (T3) strains results from the apopto

244 ontrol cell line (HEK293) were infected with reovirus serotype 3 strain Dearing (T3D) at 0, 0.1, 1, a

245 While all reovirus serotypes use junctional adhesion molecule-A as

246 fferences in pathogenesis displayed by these reovirus serotypes.

247 Characterization of each recombinant reovirus sheds light on muNS interactions with viral pro

248 Since reovirus shows promise as a cancer therapy, efficient re

249 Comparison with the structure of serotype 3 reovirus sigma1 bound to JAM-A reveals that both sigma1

250 al viral RNA-binding proteins, such as avian reovirus sigmaNS, are essential for virus replication, t

251 ts indicate that sigma1s is not required for reovirus spread by neural mechanisms.

252 a1s-null virus in peripheral organs to which reovirus spreads via the blood, including the heart, int

253 Infection with a reovirus strain that targets this splicing factor alters

254 ell types and assessed bloodstream spread of reovirus strain type 1 Lang (T1L), which disseminates so

255 After peroral inoculation, reovirus strain type 1 Lang replicates to high titers in

256 ormed by T3-T1M1, a productively replicating reovirus strain, and contained decreased numbers of comp

257 Reovirus strain-specific differences in induction of and

258 IFN-alpha/beta response is a determinant of reovirus strain-specific differences in induction of myo

259 enetration efficiency displayed by prototype reovirus strains and suggest that distinct portions of t

260 The prototype reovirus strains T1L and T3D exhibit differences in the

261 viral infection model that makes use of two reovirus strains that infect the intestine but differ in

262 , in studies of the differential capacity of reovirus strains type 1 Lang and type 3 Dearing to repli

263 d induction of myocarditis between different reovirus strains.

264 capping provides nontraditional functions to reovirus, such as promoting assembly and infectious-RNA

265 capping provides nontraditional functions to reovirus, such as promoting assembly and infectious-RNA

266 AM-A but not hematopoietic JAM-A facilitates reovirus T1L bloodstream entry and egress.

267 Indeed, RNA sequencing revealed that reovirus T1L, but not T3D, infection alters the splicing

268 To test this idea, we generated recombinant reoviruses that encoded deletions within this loop (Delt

269 vestigate the anti-cancer killing effects of reovirus therapy combined with protoporphyrin IX (PpIX)-

270 surface expression of JAM-A or attachment of reovirus to cells.

271 Attachment of reovirus to host cells is mediated by the sigma1 protein

272 operties of sigma1 influence the capacity of reovirus to target specific host tissues and produce dis

273 The pathway used by reovirus to traverse the endocytic compartment is largel

274 y endosomes with a concomitant impairment of reovirus transit to late endosomes and a delay in reovir

275 es using recombinant virus strains show that reovirus tropism for MDCK cells is primarily regulated b

276 To address this question, we use MNV and reovirus, two enteric viruses that replicate in differen

277 ng attachment and internalization, mammalian reoviruses undergo intracellular proteolytic disassembly

278 , IFITM3, localizes to late endosomes, where reoviruses undergo proteolytic disassembly; therefore, w

279 hin organelles of the endocytic compartment, reovirus undergoes stepwise disassembly catalyzed by cat

280 Within the endocytic compartment, reovirus undergoes stepwise disassembly, which is follow

281 These results suggest that reovirus uses different capsid components to bind distin

282 st this hypothesis, we engineered a panel of reovirus variants with T3A sigma3 polymorphisms introduc

283 tis virus, measles virus, influenza A virus, reovirus, vesicular stomatitis virus, human immunodefici

284 omic-resolution cryoEM map of the grass carp reovirus virion, a member of the Aquareovirus genus of t

285 ements thought to stabilize a single-shelled reovirus virion, suggesting what may be the minimal numb

286 Reovirus virions bind to soluble JAM-A and NgR1, while i

287 Together, these data suggest that reovirus virions can use both dynamin-dependent and dyna

288 Entry of reovirus virions has been well studied in several tissue

289 Thus, reovirus virions localize to early, late, and recycling

290 In vitro incubation of reovirus virions with high concentration of chymotrypsin

291 Incubating reovirus virions with soluble NgR1 neutralizes infectivi

292 neither inhibitor impedes internalization of reovirus virions, both inhibitors target virions to lyso

293 veolar endocytosis also reduced infection by reovirus virions.

294 nding suggests that sigma1s is essential for reovirus virulence when inoculated at a site that requir

295 Here, using mammalian reovirus, we highlight the molecular mechanism by which

296 s contributes to neuropathogenesis of type 3 reoviruses, which disseminate by both vascular and neura

297 nant of hematogenous dissemination by type 1 reoviruses, which reach the central nervous system (CNS)

298 FAKV is a naturally occurring single-shelled reovirus with a unique virion architecture that lacks se

299 Reovirus with PpIX-mediated photodynamic therapy resulte

300 Genomes from mammalian reoviruses with 5'pp termini, 5'pp-RNA isolated from yea