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CORD-19:61803c63a48fdddedfd407f8d440fe6b19b4a238 JSONTXT 8 Projects

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Id Subject Object Predicate Lexical cue
T1 0-159 Sentence denotes Antiviral effects of Lactobacillus ruminis SPM0211 and Bifidobacterium longum SPM1205 and SPM1206 on rotavirus-infected Caco-2 cells and a neonatal mouse model
T2 161-169 Sentence denotes Abstract
T3 170-303 Sentence denotes Rotavirus is worldwide cause of severe gastroenteritis including severe diarrhea and fatal dehydration in infants and young children.
T4 304-417 Sentence denotes There is an available vaccination program for preventing rotavirus infection, but it has limits and restrictions.
T5 418-535 Sentence denotes Probiotics therapy could be an alternative method of antiviral prevention and modulation against rotavirus infection.
T6 536-692 Sentence denotes In this study, we screened the antiviral activity of probiotic bacteria such as 3 Lactobacillus spp. and 14 Bifidobacterium spp. isolated from young Korean.
T7 693-854 Sentence denotes Three of the bacteria, Lactobacillus ruminis SPM0211, Bifidobacterium longum SPM1205, and SPM1206, inhibited human strain Wa rotavirus infection in Caco-2 cells.
T8 855-969 Sentence denotes Furthermore, these bacterial strains inhibited rotavirus replication in a rotavirus-infected neonatal mouse model.
T9 970-1121 Sentence denotes To clarify the mechanism of inhibition, we investigated gene expression of Interferon (IFN)-signaling components and IFN-inducible antiviral effectors.
T10 1122-1197 Sentence denotes All 3 probiotics increased IFN-α and IFNβ levels compared with the control.
T11 1198-1294 Sentence denotes Gene expression of IFNsignaling components and IFN-inducible antiviral effectors also increased.
T12 1295-1442 Sentence denotes Overall, these results indicate that L. ruminis SPM0211, B. longum SPM1205 and 1206 efficiently inhibit rotavirus replication in vitro and in vivo.
T13 1443-1529 Sentence denotes Especially, the antiviral effect of Lactobacillus ruminis SPM0211 is worthy of notice.
T14 1530-1593 Sentence denotes This is the first report of L. ruminis with antiviral activity.
T15 1594-1776 Sentence denotes Anti-rotaviral effects of the 3 probiotics are likely due to their modulation of the immune response through promoting type I IFNs, which are key regulators in IFN signaling pathway.
T16 1778-1865 Sentence denotes Rotavirus is a worldwide cause of severe gastroenteritis in infants and young children.
T17 1866-1984 Sentence denotes It occur a range of clinical symptoms including severe diarrhea, vomiting causing fatal dehydration, shock, and death.
T18 1985-2096 Sentence denotes The symptoms normally disappear within 3-7 days, but may last for up to 2-3 weeks (Desselberger et al., 2009) .
T19 2097-2321 Sentence denotes Antiviral therapy is not currently available for the treatment of rotavirus gastroenteritis; fluid replacement and zinc administration have been used to prevent dehydration and treat severe diarrhea (Chandran et al., 2010) .
T20 2322-2421 Sentence denotes As one of the prevention, rotavirus vaccines are licensed in many countries and are used routinely.
T21 2422-2495 Sentence denotes The incidence rate of rotavirus disease seems similar all over the world.
T22 2496-2663 Sentence denotes However, the mortality rate is due to vaccination, fatalities are rare in young children in developed countries (Parashar et al., 2009; Chen et al., 2012; WHO, 2013) .
T23 2664-2774 Sentence denotes Rotavirus vaccines are safe and efficient for preventing rotavirus gastroenteritis, although they have limits.
T24 2775-2845 Sentence denotes The vaccination programs have difficulty distribution because of cost.
T25 2846-2940 Sentence denotes So, new prevention or treatment agents to modulate rotavirus infectious disease are necessary.
T26 2941-3128 Sentence denotes Alternative method of antiviral agents is suggested application of probiotic bacteria (Chai et al., 2013; Kwak et al., 2013; Lee et al., 2013; Kim et al., 2014; Lehtoranta et al., 2014) .
T27 3129-3261 Sentence denotes Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host (FAO/WHO, 2001) .
T28 3262-3522 Sentence denotes Probiotics, such as Lactobacillus spp. and Bifidobacterium spp., are reported multiple potential health benefits including blocking gastroenteric pathogens, enhancing immune responses, and neutralizing viruses (Rolfe, 2000; Minocha, 2009; Zhang et al., 2013) .
T29 3523-3784 Sentence denotes Preidis et al. (2011) and Sur et al. (2011) reported that probiotics such as Lactobacillus rhamnosus, L. casei, Bifidobacterium bifidum, and Streptococcus thermophilus promote the innate immune response and stimulate cellular multiplication of epithelial cells.
T30 3785-3991 Sentence denotes Recently, some researchers reported that probiotics are effective in the treatment of rotavirus gastroenteritis (Dubey et al., 2008; Maragkoudakis et al., 2010; Ventola et al., 2012; Vlasova et al., 2013) .
T31 3992-4121 Sentence denotes In this study, we screened the antiviral activity of 3 Lactobacillus spp. and 14 Bifidobacterium spp. isolated from young Korean.
T32 4122-4241 Sentence denotes These probiotics were evaluated the antiviral activity with rotavirus-infected Caco-2 cells and a neonatal mouse model.
T33 4242-4381 Sentence denotes Continuously, we investigated how probiotics suppress rotavirus infection using quantitative real time polymerase chain reaction (RT-qPCR).
T34 4382-4518 Sentence denotes The human colon adenocarcinoma cell line Caco-2 and the rhesus monkey kidney cell line Vero were obtained from the Korea Cell Line Bank.
T35 4519-4742 Sentence denotes Caco-2 cells were grown in Minimum Essential Medium (MEM, Gibco Invitrogen) containing 10% fetal bovine serum (FBS, Gibco Invitrogen), 100 U/ml penicillin and 100 U/ml streptomycin at 37°C in a humidified 5% CO 2 incubator.
T36 4743-4950 Sentence denotes Vero cells were grown in Roswell Park Memorial Institute 1640 medium (RPMI 1640, Gibco Invitrogen) containing 10% FBS, 100 U/ml penicillin and 100 U/ml streptomycin at 37°C in a humidified 5% CO 2 incubator.
T37 4951-5051 Sentence denotes Human rotavirus Wa strain (HRV, KBPV-VR-47) was obtained from the Korea Bank for Pathogenic Viruses.
T38 5052-5130 Sentence denotes Viruses were propagated in Vero cells and harvested by freeze-thawing 3 times.
T39 5131-5279 Sentence denotes HRV were concentrated by ultracentrifugation, and the titer was determined as 1.5 × 10 5 plaque forming unit (PFU)/ml by plaque assay on Vero cells.
T40 5280-5326 Sentence denotes The virus stock was stored at -80°C until use.
T41 5327-5399 Sentence denotes HRV were activated for 50 min by treatment with 5 μl/ml trypsin at 37°C.
T42 5400-5441 Sentence denotes Two probiotic bacterial genera were used:
T43 5442-5529 Sentence denotes 3 Lactobacillus spp. and 14 Bifidobacterium spp. isolated from young Korean (Table 1) .
T44 5530-5650 Sentence denotes These were cultured at 37°C for 48 h in general anaerobic medium (GAM) broth (Nissui Pharm.) under anaerobic conditions.
T45 5651-5884 Sentence denotes For the preparation of probiotic bacterial extracts, cells were harvested during the exponential growth phase by centrifugation at 4,000 rpm for 10 min, washed with phosphate buffered saline (PBS), and resuspended in the same buffer.
T46 5885-6032 Sentence denotes The bacterial suspensions were adjusted to a final concentration of 1 × 10 9 colony forming unit (CFU)/ml and sonicated for 6 min (amplitude 100%).
T47 6033-6098 Sentence denotes Cell extracts were used for further experiments after filtration.
T48 6099-6267 Sentence denotes BALB/c dams and their 7 day-old pups were obtained from Koatech and housed in static microisolator cages on a special rack that delivers HEPA filtered air to each cage.
T49 6268-6309 Sentence denotes Food and water were available ad libitum.
T50 6310-6557 Sentence denotes This study was approved by the Duksung Women's University Institutional Animal Care and Use Committee (2013-007-003), and the experiments were performed in accordance with the guidelines of Duksung Women's University Policy on Animal Care and Use.
T51 6558-6751 Sentence denotes Mice were divided randomly into five groups; the negative control group received PBS, the three test groups received SPM0211, SPM1205 or SPM1206, respectively and the other is the normal group.
T52 6752-6876 Sentence denotes The mice were inoculated with extract of Wa rotavirus (1 × 10 9 PFU/ml, 150-200 μl) via oral gavage over 5 consecutive days.
T53 6877-6961 Sentence denotes The normal control group was segregated from the other animals to prevent infection.
T54 6962-7008 Sentence denotes Weight was recorded every day until sacrifice.
T55 7009-7117 Sentence denotes Fecal samples were collected from each mouse and tested for rotavirus infection using a diagnostic kit (SD).
T56 7118-7277 Sentence denotes Once the virus was detected, the three probiotics, extract of SPM0211, SPM1205, and SPM1206 (1 × 10 9 CFU/ml, 150-200 μl), were administered orally for 3 days.
T57 7278-7416 Sentence denotes Animals were sacrificed, feces were carefully removed from the colon and rectum, and the gastrointestinal tract was collected and weighed.
T58 7417-7482 Sentence denotes Specimens were rinsed twice with sterile PBS and stored at -80°C.
T59 7483-7656 Sentence denotes The cytotoxicity of the probiotic bacterial strains on cultured cells was assessed using the MTT [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide] (Sigma) assay.
T60 7657-7837 Sentence denotes Vero cells were seeded on 96-well plates at a density of 1 × 10 4 cells/well with 10% (v/v) extracts of the 3 Lactobacillus spp. and 14 Bifidobacterium spp. and incubated for 24 h.
T61 7838-7892 Sentence denotes Cells with media alone were used as the control group.
T62 7893-7977 Sentence denotes The incubation medium was removed and 100 μl of MTT solution was added to each well.
T63 7978-8104 Sentence denotes After incubation for 4 h at 37°C, the MTT solution was removed and 100 μl of dimethyl sulfoxide (DMSO) was added to each well.
T64 8105-8166 Sentence denotes Viable cells were detected by measuring absorbance at 540 nm.
T65 8167-8211 Sentence denotes Vero cells were cultured in six-well plates.
T66 8212-8386 Sentence denotes Cells were inoculated with trypsin-activated HRV (1.5 × 10 5 PFU/ml) or 10% (v/v) extracts of the 3 Lactobacillus spp. or 14 Bifidobacterium spp. for 2 h at 37°C with 5% CO2.
T67 8387-8444 Sentence denotes The inoculum was removed, and cells were washed with PBS.
T68 8445-8550 Sentence denotes The cells were covered with 2 ml of overlay media consisting of 3% agarose, 2.5% FBS and RPMI 1640 media.
T69 8551-8644 Sentence denotes After the overlay media hardened, the cells were incubated for 48-72 h at 37°C with 5% CO 2 .
T70 8645-8752 Sentence denotes The overlay media were removed, and the cells were stained with crystal violet to observe plaque formation.
T71 8753-8870 Sentence denotes We selected 3 probiotic bacteria, SPM0211, SPM1205, and SPM-1206, based on the results of plaque assay on Vero cells.
T72 8871-8972 Sentence denotes The three selected probiotic bacteria were used in a plaque assay on Caco-2 cells as described above.
T73 8973-9147 Sentence denotes Total cellular RNA was extracted from HRV-infected Caco-2 cells using QIAamp Viral RNA Mini Kit and the RNeasy Mini Kit (Qiagen) according to the manufacturer's instructions.
T74 9148-9215 Sentence denotes The intestinal tissues were homogenized using a tissue homogenizer.
T75 9216-9426 Sentence denotes Total RNA was isolated from the tissues using RNeasy Mini Kit (Qiagen) and reverse transcribed into cDNA with the Omniscript Reverse Transcription kit (Qiagen) according to with the manufacturer's instructions.
T76 9427-9477 Sentence denotes The cDNA was used as a template for real-time PCR.
T77 9478-9663 Sentence denotes A real-time PCR reaction mixture was carried out in 25 μl reaction mixtures consisting of 12.5 μl of master mix, 1 μl of each primer, 2 μl of cDNA template, and 8.5 μl of sterile water.
T78 9664-9756 Sentence denotes Master mix was prepared using Power Master SYBR ® Green PCR Master Mix (Applied Biosystems).
T79 9757-9784 Sentence denotes The human PCR primers were:
T80 9785-9794 Sentence denotes Rota VP7:
T81 9795-9892 Sentence denotes Sense, 5 -GGCTTTAAAAGAGAGAATTTCCG TCTCG-3 ; antisense, 5 -GGTCACATCATACAATTCTA ATCTAAG-3 , GAPDH:
T82 9893-9967 Sentence denotes Sense, 5 -CCATCACCATCTTCC AGGAG-3 ; antisense, 5 -CCTGCTTCACCACCTTCTTG-3 .
T83 9968-10002 Sentence denotes The murin PCR primers were: IFN-α:
T84 10003-10085 Sentence denotes Sense, 5 -CCTGT GTGATGCAACAGGTC-3 ; antisense, 5 -TCACTCCTCC TTGCTCAATC-3 , IFN-β:
T85 10086-10171 Sentence denotes Sense, 5 -ATGAACAACAGGT GGATCCTCC-3 ; antisense, 5 -AGGAGCTCCTGACATT TCCGAA-3 , IFNR:
T86 10172-10246 Sentence denotes Sense, 5 -CATGTGTGCTTCCCACC ACT-3 ; antisense, 5 -TGGAATAGTTGCCCGAGTCC-3 ,
T87 10247-10396 Sentence denotes 6 cell/ml) were simultaneously infected with 400 μl of rotavirus and treated with extract of probiotic bacteria [1 × 10 9 CFU/ml, 10% (v/v)] for 2 h.
T88 10397-10447 Sentence denotes Antiviral activity was determined by plaque assay.
T89 10448-10507 Sentence denotes We repeated the independent experiment at least five times.
T90 10508-10552 Sentence denotes The highest and lowest values were excluded.
T91 10553-10591 Sentence denotes Values shown represents the mean ± SD.
T92 10592-10807 Sentence denotes Significant differences, * P<0.05, ** P<0.01 Caco-2 cells (5 × 10 6 cell/ml) were simultaneously infected with 400 μl of rotavirus and treated with extract of probiotic bacteria [1 × 10 9 CFU/ml, 10% (v/v)] for 2 h.
T93 10808-10858 Sentence denotes Antiviral activity was determined by plaque assay.
T94 10859-10918 Sentence denotes We repeated the independent experiment at least five times.
T95 10919-10963 Sentence denotes The highest and lowest values were excluded.
T96 10964-11002 Sentence denotes Values shown represents the mean ± SD.
T97 11003-11054 Sentence denotes Significant differences, * P<0.05, ** P<0.01 STAT1:
T98 11055-11143 Sentence denotes Sense, 5 -CCATGCAAATCAGACAGTACCTGGC-3 ; antisense, 5 -CCTTCACATTTCTGACTTTACTGTC-3 , OAS:
T99 11144-11222 Sentence denotes Sense, 5 -GGATGCCTGGGAGAGAATCG-3 ; antisense, 5 -TCGCCTGCTCTTCGAAACTG-3 , Mx1:
T100 11223-11302 Sentence denotes Sense, 5 -TCTGAGGAGAGCCAGACGAT-3 ; antisense, 5 -ACT CTGGTCCCCAATGACAG-3 , PKR:
T101 11303-11385 Sentence denotes Sense, 5 -GCACCG GGTTTTGT-ATCGA-3 ; antisense, 5 -GGAGCACGAAG TACAAGCGC-3 , GAPDH:
T102 11386-11463 Sentence denotes Sense, 5 -ACGGCCGCATCT TCTTGTGCA-3 ; antisense, 5 -ACGGCCAAATCCGTTC ACACC-3 .
T103 11464-11592 Sentence denotes Real-time quantitative PCR was conducted in an Applied biosystems ® Step One Plus TM Real-Time PCR Systems (Applied Biosystems).
T104 11593-11660 Sentence denotes GAPDH which are housekeeping genes, were used as internal controls.
T105 11661-11720 Sentence denotes We repeated the independent experiment at least five times.
T106 11721-11765 Sentence denotes The highest and lowest values were excluded.
T107 11766-11876 Sentence denotes Relative quantification of the target gene was calculated using the DDCT method (Livak and Schmittgen, 2001) .
T108 11877-11933 Sentence denotes Values were expressed as mean ± standard deviation (SD).
T109 11934-12004 Sentence denotes Statistical significance was assessed at P < 0.05 for all comparisons.
T110 12005-12115 Sentence denotes Statistical analysis was performed with Statistical Product and Service Solutions (SPSS) statistical software.
T111 12116-12214 Sentence denotes Using the MTT assay, we investigated the cytotoxicity of probiotic bacteria strains on Vero cells.
T112 12215-12325 Sentence denotes Cell viability after treatment with probiotic extract showed about 80% compared with control group (Table 1) .
T113 12326-12528 Sentence denotes Initially, 3 Lactobacillus spp. and 14 Bifidobacterium spp. isolated from young Korean were used to perform plaque assays on Vero cells to select the probiotic strain with the highest inhibitory effect.
T114 12529-12657 Sentence denotes Three strains, SPM0211, SPM1205, and SPM1206, suppressed Wa rotavirus infection in Vero cells compared to the control (Fig. 1) .
T115 12658-12859 Sentence denotes Lactobacillus ruminis SPM- Caco-2 cells (5 × 10 6 cell/ml) were infected with 400 μl of rotavirus for 2 h followed by treatment with extract of probiotic bacteria [1 × 10 9 CFU/ml, 10% (v/v)] for 24 h.
T116 12860-12919 Sentence denotes We repeated the independent experiment at least five times.
T117 12920-12964 Sentence denotes The highest and lowest values were excluded.
T118 12965-13003 Sentence denotes Values shown represents the mean ± SD.
T119 13004-13097 Sentence denotes Significant differences, * P<0.05, ** P<0.01 0211 inhibited rotavirus infection by about 50%.
T120 13098-13201 Sentence denotes Bifidobacterium longum SPM1206 and SPM1205 reduced plaque formation to about 32% and 17%, respectively.
T121 13202-13296 Sentence denotes Based on these results, we selected these 3 probiotic bacteria, SPM0211, SPM1205, and SPM1206.
T122 13297-13482 Sentence denotes We carried out plaque assays with B. longum SPM1205, SPM-1206, and L. ruminis SPM0211 on Caco-2 cells as described above using either 1 × 10 8 CFU/ml or 1 × 10 9 CFU/ml of each strains.
T123 13483-13636 Sentence denotes SPM0211, SPM1205, and SPM1206 all demonstrated significant antiviral activity in HRV-infected Caco-2 cells (Fig. 2) , with similar results in Vero cells.
T124 13637-13708 Sentence denotes L. ruminis SPM-0211 treatment significantly decreased plaque formation.
T125 13709-13959 Sentence denotes SPM0211 at 1 × 10 8 CFU/ml dropped plaques on Caco-2 cells by 28% compared to the control, and SPM0211 at 1 × 10 9 CFU/ml decreased plaque formation a further 17%, indicating that SPM0211 dose-dependently reduced the plaque formation on Caco-2 cells.
T126 13960-14012 Sentence denotes B. longum SPM1206 showed similar results to SPM0211.
T127 14013-14203 Sentence denotes To determine whether the 3 probiotics had antiviral activity through inhibition of rotavirus replication, we evaluated rotavirus RNA expression in rotavirus-infected Caco-2 cells by RT-qPCR.
T128 14204-14352 Sentence denotes Rotavirus gene expression reflected similar results in Caco-2 cells treated with 3 probiotics (1 × 10 9 CFU/ml) after rotavirus infection (Fig. 3) .
T129 14353-14503 Sentence denotes SPM0211 decreased rotavirus gene expression by 40%; SPM-1205 and SPM1206 dropped gene expression by 28%, 30%, respectively, compared to control group.
T130 14504-14645 Sentence denotes We observed that treatment with SPM0211, SPM1205, and SPM1206 significantly inhibited rotavirus gene expression in HRV-infected Caco-2 cells.
T131 14646-14759 Sentence denotes Thus we investigated the anti- viral effects of the 3 probiotics using a rotavirus-infected neonatal mouse model.
T132 14760-14837 Sentence denotes We observed body weight of neonatal mice after rotavirus infection (Fig. 4) .
T133 14838-14938 Sentence denotes The control group lost weight from the 4 day, whereas the normal group steadily increased in weight.
T134 14939-15011 Sentence denotes These results were in agreement with the incubation period of rotavirus.
T135 15012-15137 Sentence denotes In the other groups, the weight of the mice was reduced compared to the normal group after an incubation period of rotavirus.
T136 15138-15327 Sentence denotes After administration of SPM0211, SPM1205, and SPM1206 (1 × 10 9 CFU/ml, each) in rotavirus-infected neonatal mice, the weights of the 3 groups gradually increased compared to control group.
T137 15328-15478 Sentence denotes To assess the potential antiviral activity of the 3 probiotics, we evaluated rotavirus gene expression in the rotavirus-infected neonatal mouse model.
T138 15479-15632 Sentence denotes SPM0211, SPM1205, and SPM1206 significantly inhibited rotavirus gene expression in HRV-infected neonatal mice, similar to the in vitro results (Fig. 5) .
T139 15633-15746 Sentence denotes We found that the SPM0211 group had a 56% decreased in rotavirus gene expression as compare to the control group.
T140 15747-15827 Sentence denotes SPM1205 and SPM1206 reduced rotavirus gene expression 39% and 47%, respectively.
T141 15828-15907 Sentence denotes Both groups were increased antiviral activity compare with results of in vitro.
T142 15908-16015 Sentence denotes We confirmed that SPM0211, SPM1205, and SPM1206 in-hibited rotavirus replication in a neonatal mouse model.
T143 16016-16172 Sentence denotes We examined whether the 3 probiotics inhibited rotavirus infection through a type I IFN signaling pathway in Wa rotavirus-infected neonatal mice by RT-qPCR.
T144 16173-16322 Sentence denotes We observed that SPM0211, SPM1205, and SPM1206 significantly increased IFN-α and IFN-β gene expression in rotavirus infected neonatal mice (Fig. 6) .
T145 16323-16439 Sentence denotes IFN-α and IFN-β gene expression were increased more double than control group in SPM0211 and SPM1205 treated groups.
T146 16440-16559 Sentence denotes In SPM1206 treated HRV-infected mice, IFN-α expression was significantly increased but IFN-β expression was unaffected.
T147 16560-16709 Sentence denotes We measured IFN receptor and signal transducer and activator of transcription (STAT) 1 gene expression, which is stimulated by type I IFNs (Fig. 7) .
T148 16710-16804 Sentence denotes All 3 probiotics significantly increased the levels of IFN receptor and STAT1 gene expression.
T149 16805-16849 Sentence denotes SPM0211 showed the most outstanding results.
T150 16850-17031 Sentence denotes We investigated gene expression of three IFN-inducible antiviral effectors: myxovirus resistance A (MxA), 20,50-oligoadenylate synthetase (OAS) and protein kinase R (PKR) (Fig. 8) .
T151 17032-17110 Sentence denotes MxA and OAS gene expression were increased by treatment with the 3 probiotics.
T152 17111-17193 Sentence denotes PKR expression was increased by SPM0211, but not influenced by SPM1205 or SPM1206.
T153 17194-17324 Sentence denotes Administration of probiotics is effective as an alternative treatment for moderate rotavirus gastroenteritis as a bacteriotherapy.
T154 17325-17525 Sentence denotes Recently, Guandalini (2011) and Foye et al. (2012) reported that probiotic bacteriotherapy is increasingly recognized to moderate infectious diarrhea and a mechanism to improve intestinal homeostasis.
T155 17526-17651 Sentence denotes According to Ventola et al. (2012) L. rhamnosus GG may increase rotavirus clear-ance from the body and reduce colon swelling.
T156 17652-17791 Sentence denotes Vlasova et al. (2013) reported that L. rhamnosus GG and B. lactis Bb12 moderate rotavirus-associated diarrhea in neonatal gnotobiotic pigs.
T157 17792-18105 Sentence denotes A number of pediatric clinical trials were reported that L. acidophilus, L. paracasei, L. rhamnosus GG, L. reuteri, S. thermophilus, and the probiotic mixture (VSL3) have significant effects on the treatment of diarrhea in children (Guandalini et al., 2000; Sarker et al., 2005; Dubey, 2008; Misra et al., 2009) .
T158 18106-18235 Sentence denotes These studies clearly show that probiotics and its metabolites are good alternatives as low cost prevention and treatment agents.
T159 18236-18408 Sentence denotes In this study, we screened the antiviral effects of 3 Lactobacillus spp. and 14 Bifidobacterium spp. isolated from young Korean against Wa rotavirus in infected Vero cells.
T160 18409-18653 Sentence denotes We selected 3 probiotic bacteria, Lactobacillus ruminis SPM0211, Bifidobacterium longum SPM1205 and SPM1206, that showed the highest inhibitory effect against Wa rotavirus based on the results of a plaque assay on rotavirus-infected Vero cells.
T161 18654-18747 Sentence denotes These probiotics showed significant antiviral activity in Wa rotavirus infected Caco-2 cells.
T162 18748-18820 Sentence denotes SPM0211 decreased plaque formation by 45% compared to the control group.
T163 18821-18884 Sentence denotes SPM1205 and 1206 were also inhibited 10% and 23%, respectively.
T164 18885-19042 Sentence denotes According to Colbère-Garapin et al. (2007) probiotics could block viral attachment at the surface of intestinal cells by competitive inhibition during entry.
T165 19043-19175 Sentence denotes However, these results did not confirm whether the probiotics inhibited rotavirus replication through modulation of the viral cycle.
T166 19176-19292 Sentence denotes Therefore, we evaluated rotavirus RNA expression by treating Wa-infected Caco-2 cells with each of the 3 probiotics.
T167 19293-19386 Sentence denotes All 3 probiotics demonstrated antiviral activity through inhibition of rotavirus replication.
T168 19387-19475 Sentence denotes SPM0211 showed the most beneficial effects (40% inhibition) against rotavirus infection.
T169 19476-19574 Sentence denotes SPM-1205 and SPM1206 dropped gene expression by 28%, 30%, respectively, compared to control group.
T170 19575-19698 Sentence denotes Taken together, these results revealed that SPM0211, SPM1205, and SPM1206 inhibited Wa rotavirus replication and infection.
T171 19699-19831 Sentence denotes We further investigated the antiviral effects of the 3 probiotics against rotavirus using a rotavirus-infected neonatal mouse model.
T172 19832-19990 Sentence denotes The control group infected rotavirus lost weight from the fourth day after administration of rotavirus, whereas the normal group steadily increased in weight.
T173 19991-20103 Sentence denotes In the SPM0211 and SPM1205 administrated group, the rate of weight gain gradually increased without weight loss.
T174 20104-20240 Sentence denotes Although SPM1206 group lost weight from the fifth day, the rate of weight loss was small and the duration was short compared to control.
T175 20241-20334 Sentence denotes We evaluated rotavirus gene expression to confirm the antiviral activity of the 3 probiotics.
T176 20335-20435 Sentence denotes The SPM0211 group had a 56% decreased in rotavirus gene expression as compared to the control group.
T177 20436-20516 Sentence denotes SPM1206 and SPM1205 reduced rotavirus gene expression 39% and 47%, respectively.
T178 20517-20645 Sentence denotes SPM1205, SPM1206, and SPM0211 had similarly antiviral activity through inhibition of rotavirus replication in vitro and in vivo.
T179 20646-20758 Sentence denotes These results indicated that all 3 probiotics might inhibit rotavirus infection and reduce symptom and duration.
T180 20759-20879 Sentence denotes Rotavirus induces inflammation by activating the cytokine response in intestinal epithelial cells (Rollo et al., 1999) .
T181 20880-20946 Sentence denotes Interferon is a representative cytokine activated by inflammation.
T182 20947-21125 Sentence denotes Type I IFNs, including IFN-α and IFN-β, are key components of the host defense against viral infections and possess pow-erful antiviral properties (Randall and Goodbourn, 2008) .
T183 21126-21265 Sentence denotes IFN-α/β, released by virus-infected cells, binds to their specific IFN receptors and leads to activation of the Jak/STAT signaling pathway.
T184 21266-21470 Sentence denotes Activation of STAT1 induces an IFNmediated antiviral response through effector pathways such as the Mx GTPase pathway, the 20,50-oligoadenylate-synthetase-directed ribonuclease L pathway, the PKR pathway.
T185 21471-21674 Sentence denotes These effector pathways individually block viral transcription, degrade viral RNA, inhibit translation, and modify protein function to control all steps of viral replication (Sadler and Williams, 2008) .
T186 21675-21844 Sentence denotes Recently, it was reported that several rotavirus strains suppress IFN production in rotavirus-infected cells (Pott et al., 2011; Angel et al., 2012; Shen et al., 2013) .
T187 21845-21930 Sentence denotes IFNs have been used as anti-rotavirus agents (Feng et al., 2008; Pott et al., 2011) .
T188 21931-22080 Sentence denotes Similarly, Park et al. (2013) reported that L. plantarum DK119 exhibits antiviral effects on influenza virus infection by modulating innate immunity.
T189 22081-22211 Sentence denotes And Lee et al. (2013) reported that B. adolescentis SPM0212 inhibits hepatitis B virus through an IFN-mediated antiviral response.
T190 22212-22355 Sentence denotes As mentioned above, probiotics have the ability to moderate the immune response and antiviral activity through activation of various cytokines.
T191 22356-22565 Sentence denotes To clarify the mechanism of antiviral effect of novel probiotics, we assessed whether L. ruminis SPM0211, B. longum SPM1205 and SPM1206 inhibited rotavirus infection through an IFN-mediated antiviral response.
T192 22566-22682 Sentence denotes The results of IFN-α and IFN-β gene expressions were similar to the results of previous studies Park et al., 2013) .
T193 22683-22747 Sentence denotes All 3 probiotics significantly increased IFN-α and IFN-β levels.
T194 22748-22853 Sentence denotes We founded that IFN-signaling components were also significantly upregulated by each of the 3 probiotics.
T195 22854-22970 Sentence denotes Besides, treatment with SPM0211, SPM1205, and SPM1206 increased gene expression of IFNinducible antiviral effectors.
T196 22971-23126 Sentence denotes These results indicated that novel probiotics modulate the immune response by promoting type I IFNs, which are key regulators in the IFN signaling pathway.
T197 23127-23264 Sentence denotes Interestingly, the antiviral activity of the 3 probiotics was not congruous with the gene expression of IFNinducible antiviral effectors.
T198 23265-23398 Sentence denotes The reason of above results is predicted that rotavirus suppressed immune response by various mechanisms during the infection period.
T199 23399-23555 Sentence denotes Our data were indicated that the 3 novel probiotics have antiviral activity through modulating IFN-mediated innate immunity against the rotavirus infection.
T200 23556-23661 Sentence denotes Especially, it is worth noting that Lactobacillus ruminis SPM0211 has antiviral effect against rotavirus.
T201 23662-23765 Sentence denotes L. ruminis is known as autochthonous species in the gastrointestinal tract of humans and other mammals.
T202 23766-23902 Sentence denotes L. ruminis exists in various species, but there is lack of research on the biological activity of them relatively to other Lactobacilli.
T203 23903-24025 Sentence denotes Taweechotipatr et al. (2009) and Neville et al. (2012) demonstrated that L. ruminis exhibited immunomodulatory properties.
T204 24026-24166 Sentence denotes We previously reported the antimicrobial activity of L. ruminis SPM0211 isolated from healthy Koreans (Yun et al., 2005; Lee et al., 2011) .
T205 24167-24346 Sentence denotes Recently, some researchers isolated L. ruminis strains from various species and reported the character of them (Forde et al., 2011; Gärtner et al., 2015; O'Donnell et al., 2015) .
T206 24347-24419 Sentence denotes However, there was no report about the antiviral activity of L. ruminis.
T207 24420-24493 Sentence denotes This is the first report concerning the antiviral activity of L. ruminis.
T208 24494-24700 Sentence denotes Overall, our results indicated that L. ruminis SPM0211 and B. longum SPM1205 and 1206 efficiently inhibit rotavirus replication in Wa rotavirus-infected Caco-2 cells and in an infected neonatal mouse model.
T209 24701-24886 Sentence denotes The antiviral effects of the three probiotics are likely due to a modulation of the immune response through promoting type I IFNs, which are key regulators in the IFN signaling pathway.
T210 24887-24962 Sentence denotes Especially, the antiviral effect of L. ruminis SPM0211 is worthy of notice.
T211 24963-25026 Sentence denotes This is the first report of L. ruminis with antiviral activity.
T212 25027-25186 Sentence denotes Our data suggest B. longum SPM1205, 1206, and L. ruminis SPM0211 have the potential to be a new prevention and reliever tool against rotavirus gastroenteritis.