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PubMed_Structured_Abstracts

Id Subject Object Predicate Lexical cue
T1 128-1821 None denotes Passage of the basement membrane (BM), which forms a barrier between the epithelium and the underlying lamina propria, represents an important step in the early pathogenesis of different alphaherpesviruses. Rho GTPase signaling plays an important role in transmigration of cells across the BM during physiological and pathological processes. We reported earlier that the US3 protein kinase of the alphaherpesvirus pseudorabies virus (PRV) interferes with Rho GTPase signaling and causes a reorganization of the host cell cytoskeleton, which as a consequence, enhances viral cell-to-cell spread in epithelial cell cultures. Here, using an ex vivo system of porcine nasal respiratory mucosa explants that allows to study PRV invasion through the BM, we found that a PRV strain that lacks US3 expression (ΔUS3 PRV) showed a reduced spread in mucosal epithelium and was virtually unable to breach the BM, in contrast to isogenic wild-type (WT) or US3 rescue PRV strains. Interestingly, addition of IPA3, an inhibitor of p21-activated kinases that blocks the effects of US3 on the cytoskeleton, suppressed the ability of WT PRV to spread across the BM. In addition, artificial suppression of RhoA signaling using CPC3 (cell-permeable C3 transferase) to mimic the effects of US3 on Rho GTPase signaling, significantly increased passage of ΔUS3 PRV through the BM, whereas it did not significantly affect BM passage of WT or US3 rescue PRV. In conclusion, these data indicate that US3 plays an important role in PRV mucosal invasion across the BM, which involves its interference with Rho GTPase signaling. This is the first report describing an alphaherpesvirus protein that drives viral BM passage.
T2 1834-2869 OBJECTIVE denotes Many viruses, including alphaherpesviruses, primarily replicate in epithelial cells of surface mucosae, such as the respiratory mucosa. Some of these viruses breach the basement membrane underlying these epithelial cells to reach underlying connective tissue and blood vessels and invade the host. Hence, epithelial spread and basement membrane passage represent crucial but still poorly understood early steps in (alphaherpes)virus pathogenesis. Here, using ex vivo porcine respiratory mucosa explants, we show that the conserved US3 protein of the porcine alphaherpesvirus pseudorabies virus (PRV) is critical for passage of PRV across the basement membrane and contributes to efficient viral epithelial spread. In addition, we show that US3-mediated viral epithelial spread and passage across the basement membrane depend at least in part on the ability of this viral protein to modulate cellular Rho GTPase signaling. This is the first report that identifies an alphaherpesvirus protein that drives viral basement membrane passage.

Goldhamster2_Cellosaurus

Id Subject Object Predicate Lexical cue
T1 162-164 CVCL_E481|Transformed_cell_line|Homo sapiens denotes BM
T2 162-164 CVCL_S926|Spontaneously_immortalized_cell_line|Lates calcarifer denotes BM
T3 179-180 CVCL_6479|Finite_cell_line|Mus musculus denotes a
T4 258-260 CVCL_8754|Cancer_cell_line|Homo sapiens denotes an
T5 258-260 CVCL_H241|Cancer_cell_line|Homo sapiens denotes an
T6 335-338 CVCL_F405|Transformed_cell_line|Homo sapiens denotes Rho
T7 362-364 CVCL_8754|Cancer_cell_line|Homo sapiens denotes an
T8 362-364 CVCL_H241|Cancer_cell_line|Homo sapiens denotes an
T9 418-420 CVCL_E481|Transformed_cell_line|Homo sapiens denotes BM
T10 418-420 CVCL_S926|Spontaneously_immortalized_cell_line|Lates calcarifer denotes BM
T11 470-472 CVCL_5M23|Cancer_cell_line|Mesocricetus auratus denotes We
T12 583-586 CVCL_F405|Transformed_cell_line|Homo sapiens denotes Rho
T13 615-616 CVCL_6479|Finite_cell_line|Mus musculus denotes a
T14 672-673 CVCL_6479|Finite_cell_line|Mus musculus denotes a
T15 763-765 CVCL_8754|Cancer_cell_line|Homo sapiens denotes an
T16 763-765 CVCL_H241|Cancer_cell_line|Homo sapiens denotes an
T17 872-874 CVCL_E481|Transformed_cell_line|Homo sapiens denotes BM
T18 872-874 CVCL_S926|Spontaneously_immortalized_cell_line|Lates calcarifer denotes BM
T19 876-878 CVCL_5M23|Cancer_cell_line|Mesocricetus auratus denotes we
T20 890-891 CVCL_6479|Finite_cell_line|Mus musculus denotes a
T21 947-948 CVCL_6479|Finite_cell_line|Mus musculus denotes a
T22 1025-1027 CVCL_E481|Transformed_cell_line|Homo sapiens denotes BM
T23 1025-1027 CVCL_S926|Spontaneously_immortalized_cell_line|Lates calcarifer denotes BM
T24 1064-1066 CVCL_6D82|Cancer_cell_line|Homo sapiens denotes WT
T25 1064-1066 CVCL_Z880|Spontaneously_immortalized_cell_line|Drosophila melanogaster denotes WT
T26 1064-1066 CVCL_Z881|Spontaneously_immortalized_cell_line|Drosophila melanogaster denotes WT
T27 1064-1066 CVCL_Z882|Spontaneously_immortalized_cell_line|Drosophila melanogaster denotes WT
T28 1128-1130 CVCL_8754|Cancer_cell_line|Homo sapiens denotes an
T29 1128-1130 CVCL_H241|Cancer_cell_line|Homo sapiens denotes an
T30 1148-1157 CVCL_C410|Hybridoma|Mus musculus denotes activated
T31 1244-1246 CVCL_6D82|Cancer_cell_line|Homo sapiens denotes WT
T32 1244-1246 CVCL_Z880|Spontaneously_immortalized_cell_line|Drosophila melanogaster denotes WT
T33 1244-1246 CVCL_Z881|Spontaneously_immortalized_cell_line|Drosophila melanogaster denotes WT
T34 1244-1246 CVCL_Z882|Spontaneously_immortalized_cell_line|Drosophila melanogaster denotes WT
T35 1272-1274 CVCL_E481|Transformed_cell_line|Homo sapiens denotes BM
T36 1272-1274 CVCL_S926|Spontaneously_immortalized_cell_line|Lates calcarifer denotes BM
T37 1357-1359 CVCL_1G32|Induced_pluripotent_stem_cell|Pan troglodytes denotes C3
T38 1357-1359 CVCL_5H89|Cancer_cell_line|Rattus norvegicus denotes C3
T39 1357-1359 CVCL_7282|Finite_cell_line|Homo sapiens denotes C3
T40 1357-1359 CVCL_DC63|Transformed_cell_line|Mus musculus denotes C3
T41 1357-1359 CVCL_JJ68|Cancer_cell_line|Homo sapiens denotes C3
T42 1376-1381 CVCL_Z366|Spontaneously_immortalized_cell_line|Spodoptera frugiperda denotes mimic
T43 1404-1407 CVCL_F405|Transformed_cell_line|Homo sapiens denotes Rho
T44 1482-1484 CVCL_E481|Transformed_cell_line|Homo sapiens denotes BM
T45 1482-1484 CVCL_S926|Spontaneously_immortalized_cell_line|Lates calcarifer denotes BM
T46 1526-1528 CVCL_E481|Transformed_cell_line|Homo sapiens denotes BM
T47 1526-1528 CVCL_S926|Spontaneously_immortalized_cell_line|Lates calcarifer denotes BM
T48 1540-1542 CVCL_6D82|Cancer_cell_line|Homo sapiens denotes WT
T49 1540-1542 CVCL_Z880|Spontaneously_immortalized_cell_line|Drosophila melanogaster denotes WT
T50 1540-1542 CVCL_Z881|Spontaneously_immortalized_cell_line|Drosophila melanogaster denotes WT
T51 1540-1542 CVCL_Z882|Spontaneously_immortalized_cell_line|Drosophila melanogaster denotes WT
T52 1612-1614 CVCL_8754|Cancer_cell_line|Homo sapiens denotes an
T53 1612-1614 CVCL_H241|Cancer_cell_line|Homo sapiens denotes an
T54 1665-1667 CVCL_E481|Transformed_cell_line|Homo sapiens denotes BM
T55 1665-1667 CVCL_S926|Spontaneously_immortalized_cell_line|Lates calcarifer denotes BM
T56 1706-1709 CVCL_F405|Transformed_cell_line|Homo sapiens denotes Rho
T57 1764-1766 CVCL_8754|Cancer_cell_line|Homo sapiens denotes an
T58 1764-1766 CVCL_H241|Cancer_cell_line|Homo sapiens denotes an
T59 1810-1812 CVCL_E481|Transformed_cell_line|Homo sapiens denotes BM
T60 1810-1812 CVCL_S926|Spontaneously_immortalized_cell_line|Lates calcarifer denotes BM
T61 1888-1897 CVCL_XY58|Transformed_cell_line|Mus musculus denotes replicate
T62 2338-2340 CVCL_5M23|Cancer_cell_line|Mesocricetus auratus denotes we
T63 2561-2563 CVCL_5M23|Cancer_cell_line|Mesocricetus auratus denotes we
T64 2734-2737 CVCL_F405|Transformed_cell_line|Homo sapiens denotes Rho
T65 2797-2799 CVCL_8754|Cancer_cell_line|Homo sapiens denotes an
T66 2797-2799 CVCL_H241|Cancer_cell_line|Homo sapiens denotes an

GoldHamster

Id Subject Object Predicate Lexical cue
T1 8-15 CHEBI:16541 denotes Protein
T2 19-31 D011557 denotes Pseudorabies
T3 19-31 D011557 denotes Pseudorabies
T4 19-37 D011558 denotes Pseudorabies Virus
T5 19-37 10345 denotes Pseudorabies Virus
T8 70-87 UBERON:0005769 denotes Basement Membrane
T7 70-87 GO:0005604 denotes Basement Membrane
T9 99-117 UBERON:0004785 denotes Respiratory Mucosa
T11 143-160 UBERON:0005769 denotes basement membrane
T10 143-160 GO:0005604 denotes basement membrane
T15 201-211 UBERON:0000483 denotes epithelium
T19 231-245 UBERON:0000030 denotes lamina propria
T20 289-301 GO:0009405 denotes pathogenesis
T21 335-338 PR:P51489 denotes Rho
T22 335-338 PR:Q03222 denotes Rho
T23 335-338 PR:P0AG30 denotes Rho
T24 335-338 PR:P15409 denotes Rho
T25 335-338 PR:P02699 denotes Rho
T26 335-338 PR:000023742 denotes Rho
T28 335-338 PR:P22328 denotes Rho
T29 335-338 PR:000001245 denotes Rho
T30 335-338 PR:P20350 denotes Rho
T31 335-338 A0A059WLZ7 denotes Rho
T32 335-338 PR:P08100 denotes Rho
T33 335-338 PR:P35359 denotes Rho
T27 335-338 CVCL_F405 denotes Rho
T34 339-345 D020558 denotes GTPase
T35 346-355 GO:0023052 denotes signaling
T36 446-468 D010335 denotes pathological processes
T37 446-468 D010335 denotes pathological processes
T38 459-468 UBERON:0004529 denotes processes
T43 503-510 SO:0000104 denotes protein
T42 503-510 PR:000000001 denotes protein
T39 503-510 GO:0003675 denotes protein
T44 503-517 D011494 denotes protein kinase
T45 525-565 10345 denotes alphaherpesvirus pseudorabies virus (PRV
T46 542-554 D011557 denotes pseudorabies
T47 542-554 D011557 denotes pseudorabies
T51 562-565 PR:000023323 denotes PRV
T52 562-565 PR:P06722 denotes PRV
T53 562-565 D011087 denotes PRV
T61 583-586 CVCL_F405 denotes Rho
T55 583-586 PR:P51489 denotes Rho
T56 583-586 PR:Q03222 denotes Rho
T57 583-586 PR:P0AG30 denotes Rho
T58 583-586 PR:P15409 denotes Rho
T59 583-586 PR:P02699 denotes Rho
T60 583-586 PR:000023742 denotes Rho
T62 583-586 PR:P22328 denotes Rho
T63 583-586 PR:000001245 denotes Rho
T64 583-586 PR:P20350 denotes Rho
T65 583-586 A0A059WLZ7 denotes Rho
T66 583-586 PR:P08100 denotes Rho
T67 583-586 PR:P35359 denotes Rho
T68 587-593 D020558 denotes GTPase
T69 594-603 GO:0023052 denotes signaling
T70 639-648 GO:0043657 denotes host cell
T71 649-661 GO:0005856 denotes cytoskeleton
T72 725-740 CL:0000066 denotes epithelial cell
T73 798-816 UBERON:0004785 denotes respiratory mucosa
T75 847-850 PR:000023323 denotes PRV
T76 847-850 PR:P06722 denotes PRV
T78 847-850 10345 denotes PRV
T77 847-850 D011087 denotes PRV
T79 892-895 PR:000023323 denotes PRV
T80 892-895 PR:P06722 denotes PRV
T82 892-895 10345 denotes PRV
T81 892-895 D011087 denotes PRV
T83 935-938 PR:000023323 denotes PRV
T84 935-938 PR:P06722 denotes PRV
T86 935-938 10345 denotes PRV
T85 935-938 D011087 denotes PRV
T87 975-985 UBERON:0000483 denotes epithelium
T88 1053-1062 SO:0000817 denotes wild-type
T89 1075-1081 SO:0000814 denotes rescue
T90 1082-1085 PR:000023323 denotes PRV
T91 1082-1085 PR:P06722 denotes PRV
T93 1082-1085 10345 denotes PRV
T92 1082-1085 D011087 denotes PRV
T94 1086-1093 D013180 denotes strains
T95 1086-1093 D013180 denotes strains
T96 1122-1125 300337 denotes IPA
T99 1122-1126 CHEBI:101355 denotes IPA3
T100 1131-1140 CHEBI:35222 denotes inhibitor
T101 1144-1147 Q07828 denotes p21
T102 1144-1147 Q62092 denotes p21
T103 1144-1147 Q11118 denotes p21
T104 1144-1147 P63028 denotes p21
T105 1144-1147 P50633 denotes p21
T106 1144-1147 O19002 denotes p21
T107 1144-1147 P50634 denotes p21
T108 1144-1147 Q08545 denotes p21
T109 1144-1147 PR:000016596 denotes p21
T110 1144-1147 P39689 denotes p21
T111 1144-1147 P61585 denotes p21
T112 1144-1147 P38936 denotes p21
T113 1144-1147 PR:Q42580 denotes p21
T114 1144-1147 Q9IV52 denotes p21
T115 1144-1147 PR:000005274 denotes p21
T116 1144-1165 D054462 denotes p21-activated kinases
T117 1204-1216 GO:0005856 denotes cytoskeleton
T118 1247-1250 PR:000023323 denotes PRV
T119 1247-1250 PR:P06722 denotes PRV
T121 1247-1250 10345 denotes PRV
T120 1247-1250 D011087 denotes PRV
T122 1289-1299 32630 denotes artificial
T123 1315-1319 PR:Q22038 denotes RhoA
T124 1315-1319 PR:000000176 denotes RhoA
T125 1315-1319 PR:Q9QUI0 denotes RhoA
T126 1315-1319 PR:P61589 denotes RhoA
T127 1315-1319 PR:P61585 denotes RhoA
T128 1315-1319 PR:P61586 denotes RhoA
T129 1320-1329 GO:0023052 denotes signaling
T130 1336-1339 C015101 denotes CPC
T135 1336-1339 C015101 denotes CPC
T133 1336-1339 P29602 denotes CPC
T134 1336-1339 PR:O22059 denotes CPC
T132 1336-1339 CL:0002664 denotes CPC
T131 1336-1339 GO:0032133 denotes CPC
T136 1360-1371 D014166 denotes transferase
T137 1376-1381 CVCL_Z366 denotes mimic
T138 1404-1407 PR:P51489 denotes Rho
T139 1404-1407 PR:Q03222 denotes Rho
T140 1404-1407 PR:P0AG30 denotes Rho
T141 1404-1407 PR:P15409 denotes Rho
T142 1404-1407 PR:P02699 denotes Rho
T143 1404-1407 PR:000023742 denotes Rho
T145 1404-1407 PR:P22328 denotes Rho
T146 1404-1407 PR:000001245 denotes Rho
T147 1404-1407 PR:P20350 denotes Rho
T148 1404-1407 A0A059WLZ7 denotes Rho
T149 1404-1407 PR:P08100 denotes Rho
T150 1404-1407 PR:P35359 denotes Rho
T144 1404-1407 CVCL_F405 denotes Rho
T151 1408-1414 D020558 denotes GTPase
T152 1415-1424 GO:0023052 denotes signaling
T153 1466-1469 PR:000023323 denotes PRV
T154 1466-1469 PR:P06722 denotes PRV
T156 1466-1469 10345 denotes PRV
T155 1466-1469 D011087 denotes PRV
T157 1550-1556 SO:0000814 denotes rescue
T158 1557-1560 PR:000023323 denotes PRV
T159 1557-1560 PR:P06722 denotes PRV
T161 1557-1560 10345 denotes PRV
T160 1557-1560 D011087 denotes PRV
T162 1633-1636 PR:000023323 denotes PRV
T163 1633-1636 PR:P06722 denotes PRV
T165 1633-1636 10345 denotes PRV
T164 1633-1636 D011087 denotes PRV
T172 1706-1709 CVCL_F405 denotes Rho
T166 1706-1709 PR:P51489 denotes Rho
T167 1706-1709 PR:Q03222 denotes Rho
T168 1706-1709 PR:P0AG30 denotes Rho
T169 1706-1709 PR:P15409 denotes Rho
T170 1706-1709 PR:P02699 denotes Rho
T171 1706-1709 PR:000023742 denotes Rho
T173 1706-1709 PR:P22328 denotes Rho
T174 1706-1709 PR:000001245 denotes Rho
T175 1706-1709 PR:P20350 denotes Rho
T176 1706-1709 A0A059WLZ7 denotes Rho
T177 1706-1709 PR:P08100 denotes Rho
T178 1706-1709 PR:P35359 denotes Rho
T179 1710-1716 D020558 denotes GTPase
T180 1717-1726 GO:0023052 denotes signaling
T185 1784-1791 SO:0000104 denotes protein
T184 1784-1791 PR:000000001 denotes protein
T181 1784-1791 GO:0003675 denotes protein
T182 1784-1791 CHEBI:36080 denotes protein
T183 1784-1791 CHEBI:11122 denotes protein
T186 1839-1846 D014780 denotes viruses
T187 1950-1968 UBERON:0004785 denotes respiratory mucosa
T189 1984-1991 D014780 denotes viruses
T191 2003-2020 UBERON:0005769 denotes basement membrane
T190 2003-2020 GO:0005604 denotes basement membrane
T196 2075-2092 UBERON:0002384 denotes connective tissue
T195 2075-2092 D003240 denotes connective tissue
T197 2075-2092 D003240 denotes connective tissue
T199 2097-2110 UBERON:0004537 denotes blood vessels
T201 2161-2178 UBERON:0005769 denotes basement membrane
T200 2161-2178 GO:0005604 denotes basement membrane
T205 2267-2279 GO:0009405 denotes pathogenesis
T206 2309-2327 UBERON:0004785 denotes respiratory mucosa
T208 2355-2364 SO:0000856 denotes conserved
T213 2369-2376 SO:0000104 denotes protein
T212 2369-2376 PR:000000001 denotes protein
T210 2369-2376 CHEBI:36080 denotes protein
T211 2369-2376 CHEBI:11122 denotes protein
T209 2369-2376 GO:0003675 denotes protein
T214 2392-2432 10345 denotes alphaherpesvirus pseudorabies virus (PRV
T215 2409-2421 D011557 denotes pseudorabies
T216 2409-2421 D011557 denotes pseudorabies
T220 2429-2432 PR:000023323 denotes PRV
T221 2429-2432 PR:P06722 denotes PRV
T222 2429-2432 D011087 denotes PRV
T227 2461-2464 10345 denotes PRV
T224 2461-2464 PR:000023323 denotes PRV
T225 2461-2464 PR:P06722 denotes PRV
T226 2461-2464 D011087 denotes PRV
T229 2476-2493 UBERON:0005769 denotes basement membrane
T228 2476-2493 GO:0005604 denotes basement membrane
T233 2634-2651 GO:0005604 denotes basement membrane
T234 2634-2651 UBERON:0005769 denotes basement membrane
T238 2699-2712 PR:000036197 denotes viral protein
T243 2705-2712 SO:0000104 denotes protein
T239 2705-2712 GO:0003675 denotes protein
T240 2705-2712 CHEBI:36080 denotes protein
T241 2705-2712 CHEBI:11122 denotes protein
T250 2734-2737 CVCL_F405 denotes Rho
T244 2734-2737 PR:P51489 denotes Rho
T245 2734-2737 PR:Q03222 denotes Rho
T246 2734-2737 PR:P0AG30 denotes Rho
T247 2734-2737 PR:P15409 denotes Rho
T248 2734-2737 PR:P02699 denotes Rho
T249 2734-2737 PR:000023742 denotes Rho
T251 2734-2737 PR:P22328 denotes Rho
T252 2734-2737 PR:000001245 denotes Rho
T253 2734-2737 PR:P20350 denotes Rho
T254 2734-2737 A0A059WLZ7 denotes Rho
T255 2734-2737 PR:P08100 denotes Rho
T256 2734-2737 PR:P35359 denotes Rho
T257 2738-2744 D020558 denotes GTPase
T258 2745-2754 GO:0023052 denotes signaling
T262 2817-2824 PR:000000001 denotes protein
T260 2817-2824 CHEBI:36080 denotes protein
T261 2817-2824 CHEBI:11122 denotes protein
T263 2817-2824 SO:0000104 denotes protein
T259 2817-2824 GO:0003675 denotes protein
T265 2843-2860 UBERON:0005769 denotes basement membrane
T264 2843-2860 GO:0005604 denotes basement membrane