Jinhua Zhang, Lei Cui, Yongliang Zhang, Hong Pan, Honggen Yuan, Saisai Zhou, Huanchun Chen, Yunfeng Song
Porcine epidemic diarrhea (PED) is a serious disease in piglets that leads to high mortality. An effective measure that provides higher IgA levels in the intestine and milk is required to decrease losses. Porcine epidemic diarrhea virus (PEDV) was dissolved in calcium alginate (Alg) and combined with chitosan (CS) via electrostatic interactions between cationic chitosan and anionic alginate to create a porous gel (Alg-CS+PEDV). The gel was used to immunize mice orally or in combination with subcutaneous injections of inactivated PEDV vaccine. At 12 and 24 days after immunization, levels of IgA and IgG in Alg-CS+PEDV were higher than with normal PEDV oral administration. At 24 days after immunization, the concentration of IFN-γ in Alg-CS+PEDV was higher than with normal PEDV oral administration. Furthermore, oral administration combining subcutaneous immunization induced higher levels of IgG and IgA than oral administration alone. Our study provides a new method for the preparation and administration of oral vaccines to achieve enhanced mucosal immunity against PEDV.
{"title":"Oral administration of PEDV-dissolved Alg-CS gel induces high and sustained mucosal immunity in mice.","authors":"Jinhua Zhang, Lei Cui, Yongliang Zhang, Hong Pan, Honggen Yuan, Saisai Zhou, Huanchun Chen, Yunfeng Song","doi":"10.1099/jgv.0.001979","DOIUrl":"https://doi.org/10.1099/jgv.0.001979","url":null,"abstract":"Porcine epidemic diarrhea (PED) is a serious disease in piglets that leads to high mortality. An effective measure that provides higher IgA levels in the intestine and milk is required to decrease losses. Porcine epidemic diarrhea virus (PEDV) was dissolved in calcium alginate (Alg) and combined with chitosan (CS) via electrostatic interactions between cationic chitosan and anionic alginate to create a porous gel (Alg-CS+PEDV). The gel was used to immunize mice orally or in combination with subcutaneous injections of inactivated PEDV vaccine. At 12 and 24 days after immunization, levels of IgA and IgG in Alg-CS+PEDV were higher than with normal PEDV oral administration. At 24 days after immunization, the concentration of IFN-γ in Alg-CS+PEDV was higher than with normal PEDV oral administration. Furthermore, oral administration combining subcutaneous immunization induced higher levels of IgG and IgA than oral administration alone. Our study provides a new method for the preparation and administration of oral vaccines to achieve enhanced mucosal immunity against PEDV.","PeriodicalId":379958,"journal":{"name":"The Journal of general virology","volume":"1119 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140774255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-07DOI: 10.1101/2023.06.06.543874
Augustine Jaccard, N. Dubuis, I. Kellenberger, J. Brodard, S. Schnée, K. Gindro, O. Schumpp
Despite the fact that Cladosporium sp. are ubiquitous fungi, their viromes have been little studied. By analysing a collection of Cladosporium fungi, two new partitiviruses named Cladosporium cladosporioides partitivirus 1 (CcPV1) and Cladosporium cladosporioides partitivirus 2 (CcPV2) co-infecting a strain of Cladosporium cladosporioides were identified. Their complete genome consists in two monocistronic dsRNA segments (RNA1 and RNA2) with a high percentage of pairwise identity on 5’ and 3’ end. The RNA dependant RNA polymerase (RdRp) of both viruses and the capsid protein (CP) of CcPV1 display the classic characteristics required for their assignment to the Gammapartitivirus genus. In contrast, CcPV2 RNA2 encodes for a 41 KDa CP that is unusually small with a low percentage of amino acid identity as compared to CPs of other viruses classified in this genus. This sequence was used to annotate fifteen similar viral sequences with unconfirmed function. The phylogeny of the CP was highly consistent with the phylogeny of their corresponding RdRp, supporting the organization of gammapartitiviruses into three distinct clades despite stretching the current demarcation criteria.
{"title":"New viruses of Cladosporium sp. expand considerably the taxonomic structure of Gammapartitivirus genus","authors":"Augustine Jaccard, N. Dubuis, I. Kellenberger, J. Brodard, S. Schnée, K. Gindro, O. Schumpp","doi":"10.1101/2023.06.06.543874","DOIUrl":"https://doi.org/10.1101/2023.06.06.543874","url":null,"abstract":"Despite the fact that Cladosporium sp. are ubiquitous fungi, their viromes have been little studied. By analysing a collection of Cladosporium fungi, two new partitiviruses named Cladosporium cladosporioides partitivirus 1 (CcPV1) and Cladosporium cladosporioides partitivirus 2 (CcPV2) co-infecting a strain of Cladosporium cladosporioides were identified. Their complete genome consists in two monocistronic dsRNA segments (RNA1 and RNA2) with a high percentage of pairwise identity on 5’ and 3’ end. The RNA dependant RNA polymerase (RdRp) of both viruses and the capsid protein (CP) of CcPV1 display the classic characteristics required for their assignment to the Gammapartitivirus genus. In contrast, CcPV2 RNA2 encodes for a 41 KDa CP that is unusually small with a low percentage of amino acid identity as compared to CPs of other viruses classified in this genus. This sequence was used to annotate fifteen similar viral sequences with unconfirmed function. The phylogeny of the CP was highly consistent with the phylogeny of their corresponding RdRp, supporting the organization of gammapartitiviruses into three distinct clades despite stretching the current demarcation criteria.","PeriodicalId":379958,"journal":{"name":"The Journal of general virology","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122778679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-13DOI: 10.1101/2022.06.13.495503
A. López-Muñoz, A. Rastrojo, Rocío Martín, A. Alcamí
The application of CRISPR/Cas9 to improve genome engineering efficiency of large dsDNA viruses has been extensively described, but a robust and versatile method for high-throughput generation of marker-free recombinants for a desire locus has not been reported yet. Cytoplasmic-replicating viruses use their own repair enzymes for homologous recombination, while nuclear-replicating viruses use the host repair machinery. This is translated into a wide range of Cas9-induced homologous recombination efficiency depending on the virus replication compartment and viral/host repair machinery characteristics and accessibility. However, the use of Cas9 as a selection agent to target parental virus genomes robustly improves the selection of desired recombinants across large dsDNA viruses. We used ectromelia virus (ECTV) and herpes simplex viruses (HSV) type 1 and 2, to optimize a CRISPR/Cas9 method that can be versatilely used for efficient genome editing and selection of both cytoplasmic- and nuclear-replicating viruses. We performed a genome-wide genetic variant analysis of mutations located at predicted off-target sequences for 20 different recombinants, showing off-target-free accuracy by deep-sequencing. Our results support this optimized method as an efficient, accurate and versatile approach to enhance the two critical factors of high-throughput viral genome engineering: generation and color-based selection of recombinants. This application of CRISPR/Cas9 reduces time and labor of screening of desired recombinants, allowing for high-throughput generation of large collections of mutant dsDNA viruses for a desire locus in less than two weeks. DATA SUMMARY Raw sequence reads are available at the European Bioinformatics Institute (EMBL-EBI) European Nucleotide Archive (ENA) as Bioproject ID PRJEB32151 and PRJEB32152. Six supplementary figures, eleven supplementary tables and supplementary methods are available with the online version of this article. The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.
{"title":"High-throughput engineering of cytoplasmic- and nuclear-replicating large dsDNA viruses by CRISPR/Cas9","authors":"A. López-Muñoz, A. Rastrojo, Rocío Martín, A. Alcamí","doi":"10.1101/2022.06.13.495503","DOIUrl":"https://doi.org/10.1101/2022.06.13.495503","url":null,"abstract":"The application of CRISPR/Cas9 to improve genome engineering efficiency of large dsDNA viruses has been extensively described, but a robust and versatile method for high-throughput generation of marker-free recombinants for a desire locus has not been reported yet. Cytoplasmic-replicating viruses use their own repair enzymes for homologous recombination, while nuclear-replicating viruses use the host repair machinery. This is translated into a wide range of Cas9-induced homologous recombination efficiency depending on the virus replication compartment and viral/host repair machinery characteristics and accessibility. However, the use of Cas9 as a selection agent to target parental virus genomes robustly improves the selection of desired recombinants across large dsDNA viruses. We used ectromelia virus (ECTV) and herpes simplex viruses (HSV) type 1 and 2, to optimize a CRISPR/Cas9 method that can be versatilely used for efficient genome editing and selection of both cytoplasmic- and nuclear-replicating viruses. We performed a genome-wide genetic variant analysis of mutations located at predicted off-target sequences for 20 different recombinants, showing off-target-free accuracy by deep-sequencing. Our results support this optimized method as an efficient, accurate and versatile approach to enhance the two critical factors of high-throughput viral genome engineering: generation and color-based selection of recombinants. This application of CRISPR/Cas9 reduces time and labor of screening of desired recombinants, allowing for high-throughput generation of large collections of mutant dsDNA viruses for a desire locus in less than two weeks. DATA SUMMARY Raw sequence reads are available at the European Bioinformatics Institute (EMBL-EBI) European Nucleotide Archive (ENA) as Bioproject ID PRJEB32151 and PRJEB32152. Six supplementary figures, eleven supplementary tables and supplementary methods are available with the online version of this article. The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.","PeriodicalId":379958,"journal":{"name":"The Journal of general virology","volume":"19 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125851118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah Klinnert, Alex Chemnitzer, P. Rusert, K. Metzner
CRISPR/dCas9-based activation systems (CRISPRa) enable sequence-specific gene activation and are therefore of particular interest for the 'shock and kill' cure approach against HIV-1 infections. This approach aims to activate the latent HIV-1 proviruses in infected cells and subsequently kill these cells. Several CRISPRa systems have been shown to specifically and effectively activate latent HIV-1 when targeted to the HIV-1 5'LTR promoter, making them a promising 'shock' strategy. Here, we aimed to evaluate the dCas9-VPR system for its applicability in reversing HIV-1 latency and identify the optimal gRNA target site in the HIV-1 5'LTR promoter leading to the strongest activation of the provirus with this system. We systematically screened the HIV-1 promoter by selecting 14 specific gRNAs that cover almost half of the HIV-1 promoter from the 3' half of the U3 until the beginning of the R region. Screening in several latently HIV-1 infected cell lines showed that dCas9-VPR leads to a high activation of HIV-1 and that gRNA-V and -VII induce the strongest activation of replication competent latent provirus. This data indicates that the optimal activation region in the HIV-1 promoter for the dCas9-VPR system is located -165 to -106 bp from the transcription start site and that it is consistent with the optimal activation region reported for other CRISPRa systems. Our data demonstrates that the dCas9-VPR system is a powerful tool for HIV-1 activation and could be harnessed for the 'shock and kill' cure approach.
{"title":"Systematic HIV-1 promoter targeting with CRISPR/dCas9-VPR reveals optimal region for activation of the latent provirus.","authors":"Sarah Klinnert, Alex Chemnitzer, P. Rusert, K. Metzner","doi":"10.1099/jgv.0.001754","DOIUrl":"https://doi.org/10.1099/jgv.0.001754","url":null,"abstract":"CRISPR/dCas9-based activation systems (CRISPRa) enable sequence-specific gene activation and are therefore of particular interest for the 'shock and kill' cure approach against HIV-1 infections. This approach aims to activate the latent HIV-1 proviruses in infected cells and subsequently kill these cells. Several CRISPRa systems have been shown to specifically and effectively activate latent HIV-1 when targeted to the HIV-1 5'LTR promoter, making them a promising 'shock' strategy. Here, we aimed to evaluate the dCas9-VPR system for its applicability in reversing HIV-1 latency and identify the optimal gRNA target site in the HIV-1 5'LTR promoter leading to the strongest activation of the provirus with this system. We systematically screened the HIV-1 promoter by selecting 14 specific gRNAs that cover almost half of the HIV-1 promoter from the 3' half of the U3 until the beginning of the R region. Screening in several latently HIV-1 infected cell lines showed that dCas9-VPR leads to a high activation of HIV-1 and that gRNA-V and -VII induce the strongest activation of replication competent latent provirus. This data indicates that the optimal activation region in the HIV-1 promoter for the dCas9-VPR system is located -165 to -106 bp from the transcription start site and that it is consistent with the optimal activation region reported for other CRISPRa systems. Our data demonstrates that the dCas9-VPR system is a powerful tool for HIV-1 activation and could be harnessed for the 'shock and kill' cure approach.","PeriodicalId":379958,"journal":{"name":"The Journal of general virology","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117266973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B. George, Rajrani Ruhel, Mohit Mazumder, V. Sharma, S. Jain, S. Gourinath, S. Chakraborty
{"title":"Corrigendum: Mutational analysis of the helicase domain of a replication initiator protein reveals critical roles of Lys 272 of the B' motif and Lys 289 of the β-hairpin loop in geminivirus replication.","authors":"B. George, Rajrani Ruhel, Mohit Mazumder, V. Sharma, S. Jain, S. Gourinath, S. Chakraborty","doi":"10.1099/jgv.0.001753","DOIUrl":"https://doi.org/10.1099/jgv.0.001753","url":null,"abstract":"","PeriodicalId":379958,"journal":{"name":"The Journal of general virology","volume":"31 5","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114050395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I. Kotta-Loizou, R. Coutts, Ictv Report Consortium
Members of the family Polymycoviridae are small viruses with multi-segmented and non-conventionally encapsidated double-stranded (ds) RNA genomes. Typically, polymycoviruses have four genomic segments, although some have up to eight. The genus Polymycovirus includes several species whose members infect fungi (ascomycetes and basidiomycetes), and oomycetes, altering host morphology, sporulation, growth and virulence. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Polymycoviridae, which is available at ictv.global/report/polymycoviridae.
{"title":"ICTV Virus Taxonomy Profile: Polymycoviridae 2022.","authors":"I. Kotta-Loizou, R. Coutts, Ictv Report Consortium","doi":"10.1099/jgv.0.001747","DOIUrl":"https://doi.org/10.1099/jgv.0.001747","url":null,"abstract":"Members of the family Polymycoviridae are small viruses with multi-segmented and non-conventionally encapsidated double-stranded (ds) RNA genomes. Typically, polymycoviruses have four genomic segments, although some have up to eight. The genus Polymycovirus includes several species whose members infect fungi (ascomycetes and basidiomycetes), and oomycetes, altering host morphology, sporulation, growth and virulence. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Polymycoviridae, which is available at ictv.global/report/polymycoviridae.","PeriodicalId":379958,"journal":{"name":"The Journal of general virology","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129382522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Sacco, Jonathan Lau, D. Godinez-Vidal, I. Kaloshian
Reverse-transcribing retroviruses exist as horizontally transmitted infectious agents or vertically transmitted endogenous retroviruses (ERVs) resident in eukaryotic genomes, and they are phylogenetically related to the long terminal repeat (LTR) class of retrotransposons. ERVs and retrotransposons are often distinguished only by the presence or absence of a gene encoding the envelope glycoprotein (env). Endogenous elements of the virus family Metaviridae include the insect-restricted Errantivirus genus of ERVs, for which some members possess env, and the pan-eukaryotic Metavirus genus that lacks an envelope glycoprotein gene. Here we report a novel Nematoda endogenous retrovirus (NERV) clade with core retroviral genes arranged uniquely as a continuous gag-env-pro-pol ORF. Reverse transcriptase sequences were phylogenetically related to metaviruses, but envelope glycoprotein sequences resembled those of the Nyamiviridae and Chrysoviridae RNA virus families, suggesting env gene capture during host cell infection by an RNA virus. NERVs were monophyletic, restricted to the nematode subclass Chromadoria, and included additional ORFs for a small hypothetical protein or a large Upf1-like RNA-dependent AAA-ATPase/helicase indicative of viral transduction of a host gene. Provirus LTR identity, low copy number, ORF integrity and segregation of three loci in Meloidogyne incognita, taken together with detection of NERV transcriptional activity, support potential infectivity of NERVs, along with their recent emergence and integration. Altogether, NERVs constitute a new and distinct Metaviridae lineage demonstrating retroviral evolution through sequential heterologous gene capture events.
{"title":"Non-canonical nematode endogenous retroviruses resulting from RNA virus glycoprotein gene capture by a metavirus.","authors":"M. Sacco, Jonathan Lau, D. Godinez-Vidal, I. Kaloshian","doi":"10.1099/jgv.0.001739","DOIUrl":"https://doi.org/10.1099/jgv.0.001739","url":null,"abstract":"Reverse-transcribing retroviruses exist as horizontally transmitted infectious agents or vertically transmitted endogenous retroviruses (ERVs) resident in eukaryotic genomes, and they are phylogenetically related to the long terminal repeat (LTR) class of retrotransposons. ERVs and retrotransposons are often distinguished only by the presence or absence of a gene encoding the envelope glycoprotein (env). Endogenous elements of the virus family Metaviridae include the insect-restricted Errantivirus genus of ERVs, for which some members possess env, and the pan-eukaryotic Metavirus genus that lacks an envelope glycoprotein gene. Here we report a novel Nematoda endogenous retrovirus (NERV) clade with core retroviral genes arranged uniquely as a continuous gag-env-pro-pol ORF. Reverse transcriptase sequences were phylogenetically related to metaviruses, but envelope glycoprotein sequences resembled those of the Nyamiviridae and Chrysoviridae RNA virus families, suggesting env gene capture during host cell infection by an RNA virus. NERVs were monophyletic, restricted to the nematode subclass Chromadoria, and included additional ORFs for a small hypothetical protein or a large Upf1-like RNA-dependent AAA-ATPase/helicase indicative of viral transduction of a host gene. Provirus LTR identity, low copy number, ORF integrity and segregation of three loci in Meloidogyne incognita, taken together with detection of NERV transcriptional activity, support potential infectivity of NERVs, along with their recent emergence and integration. Altogether, NERVs constitute a new and distinct Metaviridae lineage demonstrating retroviral evolution through sequential heterologous gene capture events.","PeriodicalId":379958,"journal":{"name":"The Journal of general virology","volume":"38 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129362409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Naveed, Muhammad Ammar Naveed, Lubna Akram, Muhammad Sharif, Mun-Il Kang, Sang-Ik Park
Species A rotavirus (RVA) is one of the pathogens causing severe acute gastroenteritis in young children and animals worldwide. RVA replicates and assembles its immature particle within electron dense compartments known as viroplasm. Despite the importance of lipid droplet (LD) formation in the RVA viroplasm, the upstream molecules modulating LD formation have remained elusive. Here, we demonstrate that RVA infection reprogrammes sterol regulatory element binding proteins (SREBPs)-dependent lipogenic pathways in virus-infected cells. Interestingly, silencing of SREBPs significantly reduced RVA protein synthesis, genome replication and progeny virus production. Moreover, knockout of SREBP-1c gene conferred resistance to RVA-induced diarrhoea, reduction of RVA replication, and mitigation of small intestinal pathology in mice. This study identifies SREBPs-mediated lipogenic reprogramming in RVA-infected host cells for facilitating virus replication and SREBPs as a potential target for developing therapeutics against RVA infection.
{"title":"Rotavirus exploits SREBP pathway for hyper lipid biogenesis during replication.","authors":"A. Naveed, Muhammad Ammar Naveed, Lubna Akram, Muhammad Sharif, Mun-Il Kang, Sang-Ik Park","doi":"10.1099/jgv.0.001757","DOIUrl":"https://doi.org/10.1099/jgv.0.001757","url":null,"abstract":"Species A rotavirus (RVA) is one of the pathogens causing severe acute gastroenteritis in young children and animals worldwide. RVA replicates and assembles its immature particle within electron dense compartments known as viroplasm. Despite the importance of lipid droplet (LD) formation in the RVA viroplasm, the upstream molecules modulating LD formation have remained elusive. Here, we demonstrate that RVA infection reprogrammes sterol regulatory element binding proteins (SREBPs)-dependent lipogenic pathways in virus-infected cells. Interestingly, silencing of SREBPs significantly reduced RVA protein synthesis, genome replication and progeny virus production. Moreover, knockout of SREBP-1c gene conferred resistance to RVA-induced diarrhoea, reduction of RVA replication, and mitigation of small intestinal pathology in mice. This study identifies SREBPs-mediated lipogenic reprogramming in RVA-infected host cells for facilitating virus replication and SREBPs as a potential target for developing therapeutics against RVA infection.","PeriodicalId":379958,"journal":{"name":"The Journal of general virology","volume":"56 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116133144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Saori Fukuda, M. Kugita, Y. Higashimoto, K. Shiogama, Hanako Tsujikawa, Kyoko Moriguchi, N. Ito, M. Sugiyama, S. Nagao, T. Murata, K. Taniguchi, S. Komoto
The group A rotavirus (RVA) genome comprising 11 double-stranded RNAs encodes six structural proteins (VP1-VP4, VP6, and VP7) and six non-structural proteins (NSP1-NSP6). Among these 12 rotaviral proteins, NSP6 has been less studied as to its function. We previously prepared a recombinant NSP6-deficient RVA derived from simian strain SA11-L2 by reverse genetics, and found that the NSP6-deficient virus grew well in cell culture, although its growth was less abundant than that of the parental SA11-L2 strain. In this study, we examined the potency of a recombinant RVA incapable of NSP6 expression to cause diarrhoea in suckling mice. The suckling mice infected with the NSP6-deficient virus apparently experienced diarrhoea, although the symptom was milder and the duration of diarrhoea was shorter than in the mice infected with the authentic SA11-L2 strain. Thus, together with the results obtained for cultured cells in the previous study, it can be concluded that NSP6 is not necessarily required for replication and pathogenicity in vitro and in vivo.
{"title":"Rotavirus incapable of NSP6 expression can cause diarrhea in suckling mice.","authors":"Saori Fukuda, M. Kugita, Y. Higashimoto, K. Shiogama, Hanako Tsujikawa, Kyoko Moriguchi, N. Ito, M. Sugiyama, S. Nagao, T. Murata, K. Taniguchi, S. Komoto","doi":"10.1099/jgv.0.001745","DOIUrl":"https://doi.org/10.1099/jgv.0.001745","url":null,"abstract":"The group A rotavirus (RVA) genome comprising 11 double-stranded RNAs encodes six structural proteins (VP1-VP4, VP6, and VP7) and six non-structural proteins (NSP1-NSP6). Among these 12 rotaviral proteins, NSP6 has been less studied as to its function. We previously prepared a recombinant NSP6-deficient RVA derived from simian strain SA11-L2 by reverse genetics, and found that the NSP6-deficient virus grew well in cell culture, although its growth was less abundant than that of the parental SA11-L2 strain. In this study, we examined the potency of a recombinant RVA incapable of NSP6 expression to cause diarrhoea in suckling mice. The suckling mice infected with the NSP6-deficient virus apparently experienced diarrhoea, although the symptom was milder and the duration of diarrhoea was shorter than in the mice infected with the authentic SA11-L2 strain. Thus, together with the results obtained for cultured cells in the previous study, it can be concluded that NSP6 is not necessarily required for replication and pathogenicity in vitro and in vivo.","PeriodicalId":379958,"journal":{"name":"The Journal of general virology","volume":"109 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133629352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrea Fořtová, V. Hönig, Martin Palus, J. Salát, M. Pýchová, L. Krbková, T. Vyhlídalová, M. Kriha, A. Chrdle, D. Růžek
Extensive axonal and neuronal loss is the main cause of severe manifestations and poor outcomes in tick-borne encephalitis (TBE). Phosphorylated neurofilament heavy subunit (pNF-H) is an essential component of axons, and its detection in cerebrospinal fluid (CSF) or serum can indicate the degree of neuroaxonal damage. We examined the use of pNF-H as a biomarker of neuroaxonal injury in TBE. In 89 patients with acute TBE, we measured CSF levels of pNF-H and 3 other markers of brain injury (glial fibrillary acidic protein, S100B and ubiquitin C-terminal hydrolase L1) and compared the results to those for patients with meningitis of other aetiology and controls. Serum pNF-H levels were measured in 80 patients and compared with findings for 90 healthy blood donors. TBE patients had significantly (P<0.001) higher CSF pNF-H levels than controls as early as hospital admission. Serum pNF-H concentrations were significantly higher in samples from TBE patients collected at hospital discharge (P<0.0001) than in controls. TBE patients with the highest peak values of serum pNF-H, exceeding 10 000 pg ml-1, had a very severe disease course, with coma or tetraplegia. Patients requiring intensive care had significantly higher serum pNF-H levels than other TBE patients (P<0.01). Elevated serum pNF-H values were also observed in patients with incomplete recovery (P<0.05). Peak serum pNF-H levels correlated positively with the duration of hospitalization (P=0.005). Measurement of pNF-H levels in TBE patients might be useful for assessing disease severity and determining prognosis.
广泛的轴突和神经元丧失是蜱传脑炎(TBE)严重表现和预后不良的主要原因。磷酸化神经丝重亚单位(phospylated neurofilament heavy subunit, pNF-H)是轴突的重要组成部分，其在脑脊液或血清中的检测可提示神经轴突的损伤程度。我们研究了pNF-H作为脑出血神经轴突损伤的生物标志物的使用。在89例急性TBE患者中，我们测量了脑脊液中pNF-H和其他3种脑损伤标志物(胶质纤维酸性蛋白、S100B和泛素c端水解酶L1)的水平，并将结果与其他病因的脑膜炎患者和对照组进行了比较。研究人员测量了80名患者的血清pNF-H水平，并与90名健康献血者的结果进行了比较。早在入院时，脑出血患者的脑脊液pNF-H水平就显著高于对照组(P<0.001)。出院时收集的TBE患者血清pNF-H浓度显著高于对照组(P<0.0001)。血清pNF-H峰值超过10000 pg ml-1的be患者病程非常严重，可出现昏迷或四肢瘫痪。重症监护患者血清pNF-H水平明显高于其他TBE患者(P<0.01)。不完全恢复患者血清pNF-H值升高(P<0.05)。峰值血清pNF-H水平与住院时间呈正相关(P=0.005)。测量TBE患者的pNF-H水平可能有助于评估疾病严重程度和确定预后。
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