PMC:7115396 / 29866-41330 JSONTXT 12 Projects

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Id Subject Object Predicate Lexical cue
T208 0-13 Sentence denotes 4 Discussion
T209 14-259 Sentence denotes Vaccines, particularly live-attenuated vaccines, remain the most effective means of protection against IBV challenge (e.g., the Mass serotype strains H120, H52, Ma5, and W93, which are still widely used in the poultry industry) [38], [39], [40].
T210 260-478 Sentence denotes However, due to the poor cross-protection provided between the different serotypes, these attenuated serotype-specific vaccines cannot provide complete protection, and the IB endemic in China cannot be controlled [22].
T211 479-639 Sentence denotes Genetic mutations and immune pressure during the replication process of the single stranded RNA virus often results in the emergence of IBV variants [41], [42].
T212 640-817 Sentence denotes To date, at least six genotypes of IBV strains have been identified in China, of which the QX-type (first isolated in 1999) remains the most prevalent genotype [10], [42], [43].
T213 818-1086 Sentence denotes The poor relationship between the QX-type strains, which are abundant and display variable virulence in various parts of China, and the Mass-type vaccine strains could explain the failure of the Mass-type vaccination programs to control IBV in these flocks [19], [39].
T214 1087-1229 Sentence denotes Consequently, the development of novel vaccines against circulating IBV strains in China using local IBV strains is required [20], [43], [44].
T215 1230-1390 Sentence denotes Optimal vaccination against circulating IBV strains in China requires the development of attenuated vaccines designed from local strains [20], [21], [22], [45].
T216 1391-1734 Sentence denotes However, due to the particularity of RNA virus replication, attenuated vaccine strains generated by continuous passage remain associated with the risk of reversion to virulence or potential recombination between vaccine strains and virulent field strains [27], [46], [47], which represents a substantial hidden concern to the poultry industry.
T217 1735-2016 Sentence denotes To reduce the problems associated with vaccine reversion, researchers have explored the option of creating vaccine viruses using reverse genetic technology (e.g., Beaudette strains carrying the S1 gene of the H120 vaccine strain, virulent M41 strain, or QX-like strain) [30], [48].
T218 2017-2201 Sentence denotes However, the titer of the Beaudette strains carrying the S1 gene of the vaccine H120 strain only reaches 106.13 ± 0.23 EID50 [49], which is lower than that of the H120 backbone strain.
T219 2202-2443 Sentence denotes Therefore, we aimed to develop a recombinant rH120-S1/YZ strain based on the H120 vaccine strain that carries the S1 gene of the ck/CH/IBYZ/2011 strain (a Chinese QX-like nephoropathogenic strain) using reverse genetic technology [35], [36].
T220 2444-2520 Sentence denotes In the present study, we isolated a nephoropathogenic strain (IBYZ) in 2011.
T221 2521-2658 Sentence denotes This strain was isolated, identified, and preserved from a large-scale chicken farm where an outbreak of IBV emerged in Jiangsu province.
T222 2659-2762 Sentence denotes Chickens infected with the IBYZ strain showed severe kidney damage and a high mortality rate (Fig. 3B).
T223 2763-2867 Sentence denotes The complete sequence has been deposited in the GenBank database under the accession number of KF663561.
T224 2868-3086 Sentence denotes The S1 gene sequencing data indicated that the IBYZ strain belonged to the QX-like genotype (Fig. 8 ), with a nucleotide homology with the attenuated vaccine H120 strain of only 77.4%, and amino acid homology of 77.1%.
T225 3087-3196 Sentence denotes Moreover, the S1/S2 cleavage site of IBYZ is HRRRR/S, which differed from RRFRR/S of the H120 vaccine strain.
T226 3197-3315 Sentence denotes After whole-genome sequencing, we constructed a molecular clone strain using reverse genetic technology, termed rIBYZ.
T227 3316-3488 Sentence denotes In addition, another strain used in this study is the live attenuated IBV vaccine, H120, and the molecular clone strain, rH120, which was constructed using the same method.
T228 3489-3660 Sentence denotes Fig. 8 Phylogenetic tree constructed based on the S1 gene of isolate ck/CH/IBYZ/2011 and 28 published IBV reference strains using the neighbor-joining method (Mega10.1.6).
T229 3661-3793 Sentence denotes The spike protein is the coronavirus structural proteins, which plays an important role on pathogenicity in coronaviruses [6], [50].
T230 3794-3905 Sentence denotes However, replacing the S gene of Beaudette strain by the virulent strains does not make it virulent [51], [52].
T231 3906-4066 Sentence denotes The S protein can be cleaved into S1 and S2 subunits at the S1/S2 cleavage site [53], the S1 subunit is responsible for receptor binding to the host cells [54].
T232 4067-4142 Sentence denotes Whether the S1 gene has an effect on the virulence of the virus is unknown.
T233 4143-4362 Sentence denotes In this study, the recombinant strain, rH120-S1/YZ, expressed the S1 gene of the QX-like strain, which retains the S1/S2 cleavage site of H120, maintained the ability to replicate and exhibited pathogenicity in embryos.
T234 4363-4456 Sentence denotes However, providing IBYZ S1 sequences to H120 did not increase its virulence to that of rIBYZ.
T235 4457-4586 Sentence denotes IBVs replicate in many epithelial cells, including respiratory tissues, the alimentary canal, kidney, gonads, and bursa [2], [6].
T236 4587-4716 Sentence denotes The QX-like rIBYZ strain is capable of considerable growth in the trachea, lung, and kidney, which leads to severe tissue damage.
T237 4717-4937 Sentence denotes In addition, this strain caused cilia necrosis and loss, lung congestion and hemorrhage, nephritis, as well as inflammatory cell infiltration in these tissues in infected chickens at different time points post-infection.
T238 4938-5211 Sentence denotes The ability of IBV to replicate within many respiratory, enteric, and other epithelial surfaces may be partially related to the fact that the attachment of IBV to host cells is dependent on sialic acid on the cell surface being recognized by the S1 subunit [6], [54], [55].
T239 5212-5347 Sentence denotes However, the binding of virus to the host cell is the first step in determining tropism and S2 is responsible for membrane fusion [56].
T240 5348-5529 Sentence denotes Thus, to further explore the different tissue tropism between rH120-S1/YZ and rIBYZ, we examined the viral loads and histopathology in the tissues of the rH120-S1/YZ-infected group.
T241 5530-5803 Sentence denotes It was found that rH120-S1/YZ remains moderately pathogenic in the trachea (e.g., some cilia necrosis and loss and decreased secretory cells) but no lesions were observed in the lungs and kidneys of infected chickens, in contrast to chickens infected with the rIBYZ strain.
T242 5804-5942 Sentence denotes This finding suggests that both the S2 and S1 genes might play an important role in viral tissue tropism as also suggested by others [57].
T243 5943-6138 Sentence denotes Another possibility is that the lack of viral replication and damage in kidney following rH120-S1/YZ is due to lower replication ability of backbone except S2 gene from its parental rH120 strain.
T244 6139-6487 Sentence denotes The viral load of the respiratory-type strain, rH120 in the different tissues indicated that the viral levels in the trachea, early following infection were significantly higher than those of rIBYZ, which indicates that the ability of the virus to attached to trachea epithelial cells of the rH120 strain was stronger than that of the rIBYZ strain.
T245 6488-6859 Sentence denotes However, during the later time points post-infection, the level of the rH120 strain was significantly lower than rIBYZ, which suggests that the virulence of IBV depends both on tissue invasion and viral replication ability, as well as other functions mediated by other viral proteins (e.g., non-structural, structural, and accessory proteins) [6], [29], [58], [59], [60].
T246 6860-7020 Sentence denotes The reduction of the viral load at 5 dpi in the group infected with the rIBYZ strain may be associated with the necrosis and shedding of the trachea epithelium.
T247 7021-7490 Sentence denotes Moreover, the ability to replication in the different organs of chickens infected with rH120-S1/YZ as reflected by viral loads at multiple time points was lower than that exhibited in the chickens infected with the rIBYZ strain, which demonstrated that the S1 subunit was not the only determinant of viral tropism that was consistent with results by others [57], [61], [62], and the significant difference in viral load was related to differences in the viral backbone.
T248 7491-7928 Sentence denotes However, when comparing the rH120-S1/YZ and rH120 strains which carry the same backbone, it was found that the viral RNA of rH120-S1/YZ in the lungs and kidneys was significantly lower than that of rH120, which may due to the replacement of the IBYZ S1 gene in the recombinant virus, whose structure on the surface contains some degree of changes, which we speculated that may affects the functionality of the S protein of coronaviruses.
T249 7929-8085 Sentence denotes Although cryo-EM structure of IBV spike protein has been determined, the relation between structure and function of different IBV S1 genes is unknown. [63].
T250 8086-8342 Sentence denotes In addition to the growth in epithelial tissues observed during the early infection period, IBV can establish long-term persistent infections in chicken flocks via oral and cloacal shedding, which represents a substantial challenge to IBV control [1], [6].
T251 8343-8488 Sentence denotes In this study, we detected viral RNA in the oral and cloacal swabs isolated from infected chickens at 7, 14, 18, 22, and 26 dpi by real-time PCR.
T252 8489-8664 Sentence denotes Compared with rH120 and rIBYZ, the viral load in both the oral and cloacal swabs of the rH120-S1/YZ group at different time points after infection was significantly decreased.
T253 8665-8866 Sentence denotes However, while it has been reported that the persistent virus will be re-excreted at the point of lay [1], the persistence of rH120-S1/YZ strain in the egg-laying chickens needs to be further verified.
T254 8867-9092 Sentence denotes In a word, due to its low virulence i presented in virus loading and lesion in different tissue, oral and cloacal shedding of host animals, rH120-S1/YZ can be considered a safe attenuated vaccine candidate for young chickens.
T255 9093-9345 Sentence denotes In addition to its role in tissue tropism, the S1 glycoprotein also has an important function in inducing a neutralizing antibody response [64], [65], and small differences in the S1 contribute to poor cross protectionby neutralization test [64], [66].
T256 9346-9556 Sentence denotes To evaluate the protective efficacy of this candidate vaccine, we selected the QX-like virulent rIBYZ strain to infect chickens at 14 dpv that were vaccinated with either the rH120-S1/YZ strain or rH120 strain.
T257 9557-9745 Sentence denotes We found that little protection against rIBYZ virulent strain challenge in the rH120 vaccinated group was induced, with a 50% survival rate and severe clinical symptoms associated with IB.
T258 9746-9837 Sentence denotes This finding could be explained by differences in the antigenicity between rH120 and rIBYZ.
T259 9838-10031 Sentence denotes No death, clinical signs, or lesions were observed in the rH120-S1/YZ-vaccinated group, indicating that this strain could provide effective protection against rIBYZ challenge in young chickens.
T260 10032-10282 Sentence denotes Since high humoral antibody titers can contribute to reduced viral replication in various organs and disease recovery [67], [68], the level of specific IgG antibodies remains an important standard for evaluating the immune response to an IBV vaccine.
T261 10283-10455 Sentence denotes In the present study, the humoral antibody level of chickens vaccinated with the rH120-S1/YZ strain was observed to gradually increase compared to the non-vaccinated group.
T262 10456-10796 Sentence denotes However, although the rH120 strain was able to induce similar levels of humoral antibodies, it provided poor protection against rIBYZ, suggesting that protection against IBV infection is not only with humoral immunity, but also with both mucosal immunity combined with the local tracheal and cellular immune response [69], [70], [71], [72].
T263 10797-10913 Sentence denotes Thus, the detection of mucosal and cellular immunity in rH120-S1/YZ-vaccinated animals requires further exploration.
T264 10914-11167 Sentence denotes Nevertheless, some studies have shown that a peptide located near the amino terminal end of S2 can be recognized by neutralizing monoclonal antibodies [73], and the S2 domain also plays an important role in inducing protective immunity [28], [61], [74].
T265 11168-11464 Sentence denotes Because the S2 domain plays an important role in cell tropism [57], we also considered that expressing the S1 subunit would provide greater safety than the entire S gene, which could lead to further destruction in some organs of the vaccinated chickens; however, further experiments are required.