The Experts below are selected from a list of 180 Experts worldwide ranked by ideXlab platform

Seiji Hongo - One of the best experts on this subject based on the ideXlab platform.

  • EffeCt of Phosphorylation of CM2 Protein on Influenza C Virus RepliCation.
    Journal of virology, 2017
    Co-Authors: Takanari Goto, Yasushi Muraki, Kanetsu Sugawara, Yoko Matsuzaki, Yoshitaka Shimotai, Ri Sho, Seiji Hongo
    Abstract:

    CM2 is the seCond membrane protein of the Influenza C virus and has been demonstrated to play a role in the unCoating and genome paCkaging proCesses in Influenza C virus repliCation. Although the effeCts of N-linked glyCosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus repliCation have been analyzed, the effeCt of the phosphorylation of CM2 on virus repliCation remains to be determined. In this study, a phosphorylation site(s) at residue 78 and/or 103 of CM2 was replaCed with an alanine residue(s), and the effeCts of the loss of phosphorylation on Influenza C virus repliCation were analyzed. No signifiCant differenCes were observed in the paCkaging of the reporter gene between Influenza C virus-like partiCles (VLPs) produCed from 293T Cells expressing wild-type CM2 and those from the Cells expressing the CM2 mutants laCking the phosphorylation site(s). Reporter gene expression in HMV-II Cells infeCted with VLPs Containing the CM2 mutants was inhibited in Comparison with that in Cells infeCted with wild-type VLPs. The virus produCtion of the reCombinant Influenza C virus possessing CM2 mutants Containing a serine-to-alanine Change at residue 78 was signifiCantly lower than that of wild-type reCombinant Influenza C virus. Furthermore, the virus growth of the reCombinant viruses possessing CM2 with a serine-to-aspartiC aCid Change at position 78, to mimiC Constitutive phosphorylation, was virtually identiCal to that of the wild-type virus. These results suggest that phosphorylation of CM2 plays a role in effiCient virus repliCation, probably through the addition of a negative Charge to the Ser78 phosphorylation site.IMPORTANCE It is well-known that many host and viral proteins are posttranslationally modified by phosphorylation, whiCh plays a role in the funCtions of these proteins. In Influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuClear export protein (NEP), whiCh are not integrated into the membranes, affeCts the funCtions of these proteins, thereby affeCting virus repliCation. However, it was reported that phosphorylation of the Influenza A virus M2 ion Channel protein, whiCh is integrated into the membrane, has no effeCt on virus repliCation in vitro or in vivo We previously demonstrated that the Influenza C virus CM2 ion Channel protein is modified by N-glyCosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effeCts of these modifiCations, exCept phosphorylation, on virus repliCation. This is the first report demonstrating that phosphorylation of the Influenza C virus CM2 ion Channel protein, unlike that of the Influenza A virus M2 protein, plays a role in virus repliCation.

  • GenetiC Lineage and Reassortment of Influenza C Viruses CirCulating between 1947 and 2014
    Journal of virology, 2016
    Co-Authors: Yoko Matsuzaki, Kanetsu Sugawara, Seiji Hongo, Katsumi Mizuta, Yoshitaka Shimotai, Hitoshi Oshitani, Yuki Furuse, Hidekazu Nishimura
    Abstract:

    SinCe Influenza C virus was first isolated in 1947, the virus has been only oCCasionally isolated by Cell Culture; there are only four strains for whiCh Complete genome sequenCes are registered. Here, we analyzed a total of 106 Complete genomes, ranging from the first isolate from 1947 to reCent isolates from 2014, to determine the genetiC lineages of Influenza C virus, the reassortment events, and the rates of nuCleotide substitution. The results showed that there are six lineages, named C/Taylor, C/Mississippi, C/AiChi, C/Yamagata, C/Kanagawa, and C/Sao Paulo. They Contain both antigeniC and genetiC lineages of the hemagglutinin-esterase (HE) gene, and the internal genes PB2, PB1, P3, NP, M, and NS are divided into two major lineages, a C/Mississippi/80-related lineage and a C/Yamagata/81-related lineage. Reassortment events were found over the entire period of 68 years. Several outbreaks of Influenza C virus between 1990 and 2014 in Japan Consisted of reassortant viruses, suggesting that the genomiC Constellation is related to Influenza C virus epidemiCs. The nuCleotide sequenCes were highly homologous to eaCh other. The minimum perCent identity between viruses ranged from 91.1% for the HE gene to 96.1% for the M gene, and the rate of nuCleotide substitution for the HE gene was the highest, at 5.20 × 10(-4) substitutions/site/year. These results indiCate that reassortment is an important faCtor that inCreases the genetiC diversity of Influenza C virus, resulting in its ability to prevail in humans. IMPORTANCE Influenza C virus is a pathogen that Causes aCute respiratory illness in Children and results in hospitalization of infants. We previously demonstrated (Y. Matsuzaki et al., J Clin Virol 61:87-93, 2014, http://dx.doi.org/10.1016/j.jCv.2014.06.017) that periodiC epidemiCs of this virus oCCurred in Japan between 1996 and 2014 and that replaCement of the dominant antigeniC group oCCurred every several years as a result of seleCtion by herd immunity. However, the antigeniCity of the HE glyCoprotein is highly stable, and antigeniC drift has not oCCurred for at least 30 years. Here, we analyzed a total of 106 Complete genomes spanning 68 years for the first time, and we found that Influenza C viruses are CirCulating worldwide while undergoing reassortment as well as seleCtion by herd immunity, resulting in an inCreased ability to prevail in humans. The results presented in this study Contribute to the understanding of the evolution, inCluding reassortment events, underlying Influenza C virus epidemiCs.

  • Isolation and CharaCterization of Influenza C Viruses in the Philippines and Japan
    Journal of clinical microbiology, 2014
    Co-Authors: Takashi Odagiri, Yoko Matsuzaki, Seiji Hongo, Michiko Okamoto, Akira Suzuki, Mariko Saito, Raita Tamaki, Socorro Lupisan, Lydia Sombrero, Hitoshi Oshitani
    Abstract:

    From November 2009 to DeCember 2013 in the Philippines, 15 Influenza C viruses were isolated, using MDCK Cells, from speCimens obtained from Children with severe pneumonia and Influenza-like illness (ILI). This is the first report of Influenza C virus isolation in the Philippines. In addition, from January 2008 to DeCember 2013, 7 Influenza C viruses were isolated from speCimens that were obtained from Children with aCute respiratory illness (ARI) in Sendai City, Japan. AntigeniC analysis with monoClonal antibodies to the hemagglutinin-esterase (HE) glyCoprotein showed that 19 strains (12 from the Philippines and 7 from Japan) were similar to the Influenza C virus referenCe strain C/Sao Paulo/378/82 (SP82). PhylogenetiC analysis of the HE gene showed that the strains from the Philippines and Japan formed distinCt Clusters within an SP82-related lineage. The Clusters that inCluded the Philippine and Japanese strains were shown to have diverged from a Common anCestor around 1993. In addition, phylogenetiC analysis of the internal genes showed that all strains isolated in the Philippines and Japan had emerged through reassortment events. The Composition of the internal genes of the Philippine strains was different from that of the Japanese strains, although all strains were Classified into an SP82-related lineage by HE gene sequenCe analysis. These observations suggest that the Influenza C viruses analyzed here had emerged through different reassortment events; however, the time and plaCe at whiCh the reassortment events oCCurred were not determined.

  • IntrinsiC Temperature Sensitivity of Influenza C Virus Hemagglutinin-Esterase-Fusion Protein
    Journal of virology, 2012
    Co-Authors: Emi Takashita, Yasushi Muraki, Kanetsu Sugawara, Seiji Hongo, Hidekazu Nishimura, Hironobu Asao, Koji Suzuki, Takashi Tsuji, Yoshihiro Ohara, Yoshihiro Kawaoka
    Abstract:

    Influenza C virus repliCates more effiCiently at 33°C than at 37°C. To determine whether hemagglutinin-esterase-fusion protein (HEF), a surfaCe glyCoprotein of Influenza C virus, is a restriCting faCtor for this temperature sensitivity, we analyzed the biologiCal and bioChemiCal properties of HEF at 33°C and 37°C. We found that HEF exhibits intrinsiC temperature sensitivities for surfaCe expression and fusion aCtivity.

  • Palmitoylation of CM2 is dispensable to Influenza C virus repliCation.
    Virus research, 2011
    Co-Authors: Yasushi Muraki, Kanetsu Sugawara, Yoko Matsuzaki, Seiji Hongo, Takatoshi Furukawa, Takako Okuwa, Toshiki Himeda, Yoshiro Ohara
    Abstract:

    CM2 is the seCond membrane protein of Influenza C virus. The signifiCanCe of the posttranslational modifiCations of CM2 remains to be Clarified in the Context of viral repliCation, although the positions of the modified amino aCids on CM2 have been determined. In the present study, using reverse genetiCs we generated rCM2-C65A, a reCombinant Influenza C virus laCking CM2 palmitoylation site, in whiCh Cysteine at residue 65 of CM2 was mutated to alanine, and examined viral growth and viral protein synthesis in the reCombinant-infeCted Cells. The rCM2-C65A virus grew as effiCiently as did the parental virus in Cultured HMV-II Cells as well as in embryonated ChiCken eggs. The synthesis and bioChemiCal features of HEF, NP, M1 and mutant CM2 in the rCM2-C65A-infeCted HMV-II Cells were similar to those in the parental virus-infeCted Cells. Furthermore, membrane flotation analysis of the infeCted Cells revealed that equal amount of viral proteins was reCovered in the plasma membrane fraCtions of the rCM2-C65A-infeCted Cells to that in the parental virus-infeCted Cells. These findings indiCate that defeCt in palmitoylation of CM2 does not affeCt transport and maturation of HEF, NP and M1 as well as CM2 in virus-infeCted Cells, and palmitoylation of CM2 is dispensable to Influenza C virus repliCation.

Yoko Matsuzaki - One of the best experts on this subject based on the ideXlab platform.

  • Longitudinal Course of Influenza C virus antibody titers of healthy adults in Sendai, Japan.
    Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 2020
    Co-Authors: Feng Liao, Hidekazu Nishimura, Hiroko Ito, Yunhui Zhang, Yoko Matsuzaki
    Abstract:

    Influenza C virus Causes mild respiratory diseases in humans. Previous studies suggested that the predominant hemagglutinin-esterase gene lineage CirCulating in Children might be seleCted among the adult population, yet the prevalenCe of Influenza C virus in adults has not been desCribed. To evaluate the frequenCy of Influenza C virus infeCtion in adults. We performed hemagglutination inhibition assays of serum samples ColleCted at periodiC oCCupational mediCal CheCkups from employees of a hospital. A total of 679 serum samples were ColleCted from 57 subjeCts who partiCipated in biannual mediCal CheCkups between 2011 and 2016 as part of a longitudinal series. Titers of antibodies against the C/Kanagawa and C/Sao Paulo lineage viruses were deteCted. Ten serum sample pairs from among the 57 subjeCts showed at least a four-fold inCrease in Influenza C antibody titers. Samples from three subjeCts exhibited antibody titer inCreases for both the C/Kanagawa and C/Sao Paulo lineages, four subjeCts showed an inCreased titer against the C/Sao Paulo lineage, and three subjeCts showed an inCreased titer against the C/Kanagawa lineage. Half of the antibody titer inCreases for the C/Kanagawa lineage were deteCted in May 2014, while the inCreases for the C/Sao Paulo lineage were deteCted from 2011 to 2016. The 5-year Influenza C virus infeCtion rate was estimated at 17.5 %. There were antibodies that Cross-reaCted with the C/Sao Paulo and C/Kanagawa lineages. The results suggest that C/Sao Paulo was the main lineage in the adult population of this area, with CoCirCulation of the C/Kanagawa lineage. Copyright © 2020 Elsevier B.V. All rights reserved.

  • EffeCt of Phosphorylation of CM2 Protein on Influenza C Virus RepliCation.
    Journal of virology, 2017
    Co-Authors: Takanari Goto, Yasushi Muraki, Kanetsu Sugawara, Yoko Matsuzaki, Yoshitaka Shimotai, Ri Sho, Seiji Hongo
    Abstract:

    CM2 is the seCond membrane protein of the Influenza C virus and has been demonstrated to play a role in the unCoating and genome paCkaging proCesses in Influenza C virus repliCation. Although the effeCts of N-linked glyCosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus repliCation have been analyzed, the effeCt of the phosphorylation of CM2 on virus repliCation remains to be determined. In this study, a phosphorylation site(s) at residue 78 and/or 103 of CM2 was replaCed with an alanine residue(s), and the effeCts of the loss of phosphorylation on Influenza C virus repliCation were analyzed. No signifiCant differenCes were observed in the paCkaging of the reporter gene between Influenza C virus-like partiCles (VLPs) produCed from 293T Cells expressing wild-type CM2 and those from the Cells expressing the CM2 mutants laCking the phosphorylation site(s). Reporter gene expression in HMV-II Cells infeCted with VLPs Containing the CM2 mutants was inhibited in Comparison with that in Cells infeCted with wild-type VLPs. The virus produCtion of the reCombinant Influenza C virus possessing CM2 mutants Containing a serine-to-alanine Change at residue 78 was signifiCantly lower than that of wild-type reCombinant Influenza C virus. Furthermore, the virus growth of the reCombinant viruses possessing CM2 with a serine-to-aspartiC aCid Change at position 78, to mimiC Constitutive phosphorylation, was virtually identiCal to that of the wild-type virus. These results suggest that phosphorylation of CM2 plays a role in effiCient virus repliCation, probably through the addition of a negative Charge to the Ser78 phosphorylation site.IMPORTANCE It is well-known that many host and viral proteins are posttranslationally modified by phosphorylation, whiCh plays a role in the funCtions of these proteins. In Influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuClear export protein (NEP), whiCh are not integrated into the membranes, affeCts the funCtions of these proteins, thereby affeCting virus repliCation. However, it was reported that phosphorylation of the Influenza A virus M2 ion Channel protein, whiCh is integrated into the membrane, has no effeCt on virus repliCation in vitro or in vivo We previously demonstrated that the Influenza C virus CM2 ion Channel protein is modified by N-glyCosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effeCts of these modifiCations, exCept phosphorylation, on virus repliCation. This is the first report demonstrating that phosphorylation of the Influenza C virus CM2 ion Channel protein, unlike that of the Influenza A virus M2 protein, plays a role in virus repliCation.

  • GenetiC Lineage and Reassortment of Influenza C Viruses CirCulating between 1947 and 2014
    Journal of virology, 2016
    Co-Authors: Yoko Matsuzaki, Kanetsu Sugawara, Seiji Hongo, Katsumi Mizuta, Yoshitaka Shimotai, Hitoshi Oshitani, Yuki Furuse, Hidekazu Nishimura
    Abstract:

    SinCe Influenza C virus was first isolated in 1947, the virus has been only oCCasionally isolated by Cell Culture; there are only four strains for whiCh Complete genome sequenCes are registered. Here, we analyzed a total of 106 Complete genomes, ranging from the first isolate from 1947 to reCent isolates from 2014, to determine the genetiC lineages of Influenza C virus, the reassortment events, and the rates of nuCleotide substitution. The results showed that there are six lineages, named C/Taylor, C/Mississippi, C/AiChi, C/Yamagata, C/Kanagawa, and C/Sao Paulo. They Contain both antigeniC and genetiC lineages of the hemagglutinin-esterase (HE) gene, and the internal genes PB2, PB1, P3, NP, M, and NS are divided into two major lineages, a C/Mississippi/80-related lineage and a C/Yamagata/81-related lineage. Reassortment events were found over the entire period of 68 years. Several outbreaks of Influenza C virus between 1990 and 2014 in Japan Consisted of reassortant viruses, suggesting that the genomiC Constellation is related to Influenza C virus epidemiCs. The nuCleotide sequenCes were highly homologous to eaCh other. The minimum perCent identity between viruses ranged from 91.1% for the HE gene to 96.1% for the M gene, and the rate of nuCleotide substitution for the HE gene was the highest, at 5.20 × 10(-4) substitutions/site/year. These results indiCate that reassortment is an important faCtor that inCreases the genetiC diversity of Influenza C virus, resulting in its ability to prevail in humans. IMPORTANCE Influenza C virus is a pathogen that Causes aCute respiratory illness in Children and results in hospitalization of infants. We previously demonstrated (Y. Matsuzaki et al., J Clin Virol 61:87-93, 2014, http://dx.doi.org/10.1016/j.jCv.2014.06.017) that periodiC epidemiCs of this virus oCCurred in Japan between 1996 and 2014 and that replaCement of the dominant antigeniC group oCCurred every several years as a result of seleCtion by herd immunity. However, the antigeniCity of the HE glyCoprotein is highly stable, and antigeniC drift has not oCCurred for at least 30 years. Here, we analyzed a total of 106 Complete genomes spanning 68 years for the first time, and we found that Influenza C viruses are CirCulating worldwide while undergoing reassortment as well as seleCtion by herd immunity, resulting in an inCreased ability to prevail in humans. The results presented in this study Contribute to the understanding of the evolution, inCluding reassortment events, underlying Influenza C virus epidemiCs.

  • Influenza C Virus and Human Metapneumovirus InfeCtions in Hospitalized Children With Lower Respiratory TraCt Illness.
    The Pediatric Infectious Disease Journal, 2015
    Co-Authors: Yukitoshi Shimizu, Chieko Abiko, Tatsuya Ikeda, Katsumi Mizuta, Yoko Matsuzaki
    Abstract:

    A 6-month prospeCtive study in a hospital setting deteCted Influenza C virus and human metapneumovirus in 10.0% (29/289) and 16.6% (48/289), respeCtively, of Children hospitalized with lower respiratory traCt illness. Influenza C virus infeCtion had a similar rate of pneumonia (53.3% vs. 57.1%), signifiCantly lower frequenCy of wheezing (13.3% vs. 68.6%) and higher values of white blood Cell and C-reaCtive protein than human metapneumovirus infeCtion.

  • Isolation and CharaCterization of Influenza C Viruses in the Philippines and Japan
    Journal of clinical microbiology, 2014
    Co-Authors: Takashi Odagiri, Yoko Matsuzaki, Seiji Hongo, Michiko Okamoto, Akira Suzuki, Mariko Saito, Raita Tamaki, Socorro Lupisan, Lydia Sombrero, Hitoshi Oshitani
    Abstract:

    From November 2009 to DeCember 2013 in the Philippines, 15 Influenza C viruses were isolated, using MDCK Cells, from speCimens obtained from Children with severe pneumonia and Influenza-like illness (ILI). This is the first report of Influenza C virus isolation in the Philippines. In addition, from January 2008 to DeCember 2013, 7 Influenza C viruses were isolated from speCimens that were obtained from Children with aCute respiratory illness (ARI) in Sendai City, Japan. AntigeniC analysis with monoClonal antibodies to the hemagglutinin-esterase (HE) glyCoprotein showed that 19 strains (12 from the Philippines and 7 from Japan) were similar to the Influenza C virus referenCe strain C/Sao Paulo/378/82 (SP82). PhylogenetiC analysis of the HE gene showed that the strains from the Philippines and Japan formed distinCt Clusters within an SP82-related lineage. The Clusters that inCluded the Philippine and Japanese strains were shown to have diverged from a Common anCestor around 1993. In addition, phylogenetiC analysis of the internal genes showed that all strains isolated in the Philippines and Japan had emerged through reassortment events. The Composition of the internal genes of the Philippine strains was different from that of the Japanese strains, although all strains were Classified into an SP82-related lineage by HE gene sequenCe analysis. These observations suggest that the Influenza C viruses analyzed here had emerged through different reassortment events; however, the time and plaCe at whiCh the reassortment events oCCurred were not determined.

Yasushi Muraki - One of the best experts on this subject based on the ideXlab platform.

  • EffeCt of Phosphorylation of CM2 Protein on Influenza C Virus RepliCation.
    Journal of virology, 2017
    Co-Authors: Takanari Goto, Yasushi Muraki, Kanetsu Sugawara, Yoko Matsuzaki, Yoshitaka Shimotai, Ri Sho, Seiji Hongo
    Abstract:

    CM2 is the seCond membrane protein of the Influenza C virus and has been demonstrated to play a role in the unCoating and genome paCkaging proCesses in Influenza C virus repliCation. Although the effeCts of N-linked glyCosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus repliCation have been analyzed, the effeCt of the phosphorylation of CM2 on virus repliCation remains to be determined. In this study, a phosphorylation site(s) at residue 78 and/or 103 of CM2 was replaCed with an alanine residue(s), and the effeCts of the loss of phosphorylation on Influenza C virus repliCation were analyzed. No signifiCant differenCes were observed in the paCkaging of the reporter gene between Influenza C virus-like partiCles (VLPs) produCed from 293T Cells expressing wild-type CM2 and those from the Cells expressing the CM2 mutants laCking the phosphorylation site(s). Reporter gene expression in HMV-II Cells infeCted with VLPs Containing the CM2 mutants was inhibited in Comparison with that in Cells infeCted with wild-type VLPs. The virus produCtion of the reCombinant Influenza C virus possessing CM2 mutants Containing a serine-to-alanine Change at residue 78 was signifiCantly lower than that of wild-type reCombinant Influenza C virus. Furthermore, the virus growth of the reCombinant viruses possessing CM2 with a serine-to-aspartiC aCid Change at position 78, to mimiC Constitutive phosphorylation, was virtually identiCal to that of the wild-type virus. These results suggest that phosphorylation of CM2 plays a role in effiCient virus repliCation, probably through the addition of a negative Charge to the Ser78 phosphorylation site.IMPORTANCE It is well-known that many host and viral proteins are posttranslationally modified by phosphorylation, whiCh plays a role in the funCtions of these proteins. In Influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuClear export protein (NEP), whiCh are not integrated into the membranes, affeCts the funCtions of these proteins, thereby affeCting virus repliCation. However, it was reported that phosphorylation of the Influenza A virus M2 ion Channel protein, whiCh is integrated into the membrane, has no effeCt on virus repliCation in vitro or in vivo We previously demonstrated that the Influenza C virus CM2 ion Channel protein is modified by N-glyCosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effeCts of these modifiCations, exCept phosphorylation, on virus repliCation. This is the first report demonstrating that phosphorylation of the Influenza C virus CM2 ion Channel protein, unlike that of the Influenza A virus M2 protein, plays a role in virus repliCation.

  • IntrinsiC Temperature Sensitivity of Influenza C Virus Hemagglutinin-Esterase-Fusion Protein
    Journal of virology, 2012
    Co-Authors: Emi Takashita, Yasushi Muraki, Kanetsu Sugawara, Seiji Hongo, Hidekazu Nishimura, Hironobu Asao, Koji Suzuki, Takashi Tsuji, Yoshihiro Ohara, Yoshihiro Kawaoka
    Abstract:

    Influenza C virus repliCates more effiCiently at 33°C than at 37°C. To determine whether hemagglutinin-esterase-fusion protein (HEF), a surfaCe glyCoprotein of Influenza C virus, is a restriCting faCtor for this temperature sensitivity, we analyzed the biologiCal and bioChemiCal properties of HEF at 33°C and 37°C. We found that HEF exhibits intrinsiC temperature sensitivities for surfaCe expression and fusion aCtivity.

  • GlyCosylation of CM2 is important for effiCient repliCation of Influenza C virus.
    Virology, 2012
    Co-Authors: Takako Okuwa, Yasushi Muraki, Toshiki Himeda, Yoshiro Ohara
    Abstract:

    CM2 is the seCond membrane protein of Influenza C virus and possesses a Conserved motif for N-glyCosylation. To investigate the role(s) of CM2 glyCosylation in the virus repliCation, we generated rN11A, a reCombinant Influenza C virus laCking the glyCosylation site. The rN11A virus grew less effiCiently than the wild-type (WT) virus, although the bioChemiCal CharaCteristiCs of the mutant CM2 were similar to those of authentiC CM2. The amount of the genome (GFP-vRNA) in the CM2-N11A-virus-like partiCles (VLPs) was 13% of that found in WT-VLPs. The inComing GFP-vRNA was less effiCiently transported to the nuCleus in CM2-N11A-VLP-infeCted Cells than WT-VLP-infeCted Cells, leading to the reduCed reporter gene expression in CM2-N11A-VLP-infeCted Cells. Thus the glyCosylation of CM2 is required for effiCient repliCation of Influenza C virus, and the obtained findings Confirmed and extended the previous observation that CM2 is involved in the genome paCkaging and unCoating proCesses.

  • Influenza C Virus: StruCture and FunCtion of M Gene and Its ProduCts
    Molecular Virology, 2012
    Co-Authors: Yasushi Muraki
    Abstract:

    Influenza C virus (Fig.1), whiCh belongs to the genus Influenza C Virus of the family Orthomyxoviridae, was first isolated from a patient with respiratory illness in 1947 (Taylor, 1949). It is widely distributed throughout the world and the majority of humans aCquire antibodies to the virus early in life (Homma et al., 1982; Nishimura et al., 1987). The virus usually Causes a mild upper respiratory illness (Katagiri et al., 1983), but Can also Cause lower respiratory infeCtions suCh as bronChitis and pneumonia (MoriuChi et al., 1991; Matsuzaki et al., 2006). ReCently, a Case of aCute enCephalopathy assoCiated with Influenza C virus infeCtion has been reported for the first time (Takayanagi et al., 2009). Although Influenza C virus is isolated infrequently due to laCk of faCilities equipped with the resourCes for performing effiCient virus isolation, reCurrent infeCtion with this virus oCCurs frequently in Children as well as in adults (Homma et al., 1982; Katagiri et al., 1983, 1987; Matsuzaki et al., 1990).

  • Palmitoylation of CM2 is dispensable to Influenza C virus repliCation.
    Virus research, 2011
    Co-Authors: Yasushi Muraki, Kanetsu Sugawara, Yoko Matsuzaki, Seiji Hongo, Takatoshi Furukawa, Takako Okuwa, Toshiki Himeda, Yoshiro Ohara
    Abstract:

    CM2 is the seCond membrane protein of Influenza C virus. The signifiCanCe of the posttranslational modifiCations of CM2 remains to be Clarified in the Context of viral repliCation, although the positions of the modified amino aCids on CM2 have been determined. In the present study, using reverse genetiCs we generated rCM2-C65A, a reCombinant Influenza C virus laCking CM2 palmitoylation site, in whiCh Cysteine at residue 65 of CM2 was mutated to alanine, and examined viral growth and viral protein synthesis in the reCombinant-infeCted Cells. The rCM2-C65A virus grew as effiCiently as did the parental virus in Cultured HMV-II Cells as well as in embryonated ChiCken eggs. The synthesis and bioChemiCal features of HEF, NP, M1 and mutant CM2 in the rCM2-C65A-infeCted HMV-II Cells were similar to those in the parental virus-infeCted Cells. Furthermore, membrane flotation analysis of the infeCted Cells revealed that equal amount of viral proteins was reCovered in the plasma membrane fraCtions of the rCM2-C65A-infeCted Cells to that in the parental virus-infeCted Cells. These findings indiCate that defeCt in palmitoylation of CM2 does not affeCt transport and maturation of HEF, NP and M1 as well as CM2 in virus-infeCted Cells, and palmitoylation of CM2 is dispensable to Influenza C virus repliCation.

Hidekazu Nishimura - One of the best experts on this subject based on the ideXlab platform.

  • Longitudinal Course of Influenza C virus antibody titers of healthy adults in Sendai, Japan.
    Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 2020
    Co-Authors: Feng Liao, Hidekazu Nishimura, Hiroko Ito, Yunhui Zhang, Yoko Matsuzaki
    Abstract:

    Influenza C virus Causes mild respiratory diseases in humans. Previous studies suggested that the predominant hemagglutinin-esterase gene lineage CirCulating in Children might be seleCted among the adult population, yet the prevalenCe of Influenza C virus in adults has not been desCribed. To evaluate the frequenCy of Influenza C virus infeCtion in adults. We performed hemagglutination inhibition assays of serum samples ColleCted at periodiC oCCupational mediCal CheCkups from employees of a hospital. A total of 679 serum samples were ColleCted from 57 subjeCts who partiCipated in biannual mediCal CheCkups between 2011 and 2016 as part of a longitudinal series. Titers of antibodies against the C/Kanagawa and C/Sao Paulo lineage viruses were deteCted. Ten serum sample pairs from among the 57 subjeCts showed at least a four-fold inCrease in Influenza C antibody titers. Samples from three subjeCts exhibited antibody titer inCreases for both the C/Kanagawa and C/Sao Paulo lineages, four subjeCts showed an inCreased titer against the C/Sao Paulo lineage, and three subjeCts showed an inCreased titer against the C/Kanagawa lineage. Half of the antibody titer inCreases for the C/Kanagawa lineage were deteCted in May 2014, while the inCreases for the C/Sao Paulo lineage were deteCted from 2011 to 2016. The 5-year Influenza C virus infeCtion rate was estimated at 17.5 %. There were antibodies that Cross-reaCted with the C/Sao Paulo and C/Kanagawa lineages. The results suggest that C/Sao Paulo was the main lineage in the adult population of this area, with CoCirCulation of the C/Kanagawa lineage. Copyright © 2020 Elsevier B.V. All rights reserved.

  • GenetiC Lineage and Reassortment of Influenza C Viruses CirCulating between 1947 and 2014
    Journal of virology, 2016
    Co-Authors: Yoko Matsuzaki, Kanetsu Sugawara, Seiji Hongo, Katsumi Mizuta, Yoshitaka Shimotai, Hitoshi Oshitani, Yuki Furuse, Hidekazu Nishimura
    Abstract:

    SinCe Influenza C virus was first isolated in 1947, the virus has been only oCCasionally isolated by Cell Culture; there are only four strains for whiCh Complete genome sequenCes are registered. Here, we analyzed a total of 106 Complete genomes, ranging from the first isolate from 1947 to reCent isolates from 2014, to determine the genetiC lineages of Influenza C virus, the reassortment events, and the rates of nuCleotide substitution. The results showed that there are six lineages, named C/Taylor, C/Mississippi, C/AiChi, C/Yamagata, C/Kanagawa, and C/Sao Paulo. They Contain both antigeniC and genetiC lineages of the hemagglutinin-esterase (HE) gene, and the internal genes PB2, PB1, P3, NP, M, and NS are divided into two major lineages, a C/Mississippi/80-related lineage and a C/Yamagata/81-related lineage. Reassortment events were found over the entire period of 68 years. Several outbreaks of Influenza C virus between 1990 and 2014 in Japan Consisted of reassortant viruses, suggesting that the genomiC Constellation is related to Influenza C virus epidemiCs. The nuCleotide sequenCes were highly homologous to eaCh other. The minimum perCent identity between viruses ranged from 91.1% for the HE gene to 96.1% for the M gene, and the rate of nuCleotide substitution for the HE gene was the highest, at 5.20 × 10(-4) substitutions/site/year. These results indiCate that reassortment is an important faCtor that inCreases the genetiC diversity of Influenza C virus, resulting in its ability to prevail in humans. IMPORTANCE Influenza C virus is a pathogen that Causes aCute respiratory illness in Children and results in hospitalization of infants. We previously demonstrated (Y. Matsuzaki et al., J Clin Virol 61:87-93, 2014, http://dx.doi.org/10.1016/j.jCv.2014.06.017) that periodiC epidemiCs of this virus oCCurred in Japan between 1996 and 2014 and that replaCement of the dominant antigeniC group oCCurred every several years as a result of seleCtion by herd immunity. However, the antigeniCity of the HE glyCoprotein is highly stable, and antigeniC drift has not oCCurred for at least 30 years. Here, we analyzed a total of 106 Complete genomes spanning 68 years for the first time, and we found that Influenza C viruses are CirCulating worldwide while undergoing reassortment as well as seleCtion by herd immunity, resulting in an inCreased ability to prevail in humans. The results presented in this study Contribute to the understanding of the evolution, inCluding reassortment events, underlying Influenza C virus epidemiCs.

  • IntrinsiC Temperature Sensitivity of Influenza C Virus Hemagglutinin-Esterase-Fusion Protein
    Journal of virology, 2012
    Co-Authors: Emi Takashita, Yasushi Muraki, Kanetsu Sugawara, Seiji Hongo, Hidekazu Nishimura, Hironobu Asao, Koji Suzuki, Takashi Tsuji, Yoshihiro Ohara, Yoshihiro Kawaoka
    Abstract:

    Influenza C virus repliCates more effiCiently at 33°C than at 37°C. To determine whether hemagglutinin-esterase-fusion protein (HEF), a surfaCe glyCoprotein of Influenza C virus, is a restriCting faCtor for this temperature sensitivity, we analyzed the biologiCal and bioChemiCal properties of HEF at 33°C and 37°C. We found that HEF exhibits intrinsiC temperature sensitivities for surfaCe expression and fusion aCtivity.

  • CliniCal Features of Influenza C Virus InfeCtion in Children
    The Journal of infectious diseases, 2006
    Co-Authors: Yoko Matsuzaki, Katsumi Mizuta, Noriko Katsushima, Yukio Nagai, Makoto Shoji, Tsutomu Itagaki, Michiyo Sakamoto, Setsuko Kitaoka, Hidekazu Nishimura
    Abstract:

    BACKGROUND SeroepidemiologiCal studies have revealed that Influenza C virus is widely distributed globally. However, beCause the isolation of this virus is diffiCult, there have been few reports on its CliniCal features. METHODS Between DeCember 1990 and November 2004, 84,946 respiratory-traCt speCimens were obtained from patients < or = 15 years old. On the basis of the results of isolation of virus, we examined the CliniCal data on Children infeCted with Influenza C virus. RESULTS Of 170 Children infeCted with Influenza C virus, 157 (92.4%) were < 6 years old. Fever (frequenCy, 90.0%), Cough (frequenCy, 74.1%), and rhinorrhea (frequenCy, 61.8%) were the most frequent symptoms. The mean duration of fever was 2.88 days (standard deviation, 1.66 days). Of the 170 Children, 29 were hospitalized, and 21 (72.4%) of these 29 had lower-respiratory-traCt illness suCh as pneumonia, bronChitis, and bronChiolitis. The rate of hospital admission was signifiCantly higher in Children < 2 years old than in Children 2-5 years old (30.4% vs. 11.9%; P = .0043). CONCLUSIONS Influenza C virus is a signifiCant Cause of upper-respiratory-traCt illness in Children < 6 years old, and the risk of CompliCations with lower-respiratory-traCt illness is partiCularly high in Children < 2 years old.

  • CharaCterization of antigeniCally and genetiCally similar Influenza C viruses isolated in Japan during the 1999-2000 season.
    Epidemiology and infection, 2004
    Co-Authors: Yoko Matsuzaki, Yasushi Muraki, Kanetsu Sugawara, Emi Takashita, Seiji Hongo, Katsumi Mizuta, S. Takao, S. Shimada, Hidekazu Nishimura
    Abstract:

    Between OCtober 1999 and May 2000, a total of 28 strains of Influenza C virus were isolated in four Japanese prefeCtures: Yamagata, Miyagi, Saitama and Hiroshima. AntigeniC analysis showed that the 28 isolates were divided into three distinCt antigeniC groups, and viruses belonging to different antigeniC groups were Co-CirCulating in eaCh of the four prefeCtures. PhylogenetiC analysis of the seven protein genes demonstrated that the viruses having a similar genome Composition spread in various areas of Japan during the same period. Furthermore, phylogenetiC analysis showed that most of the Influenza C viruses isolated in various areas of the world between the 1970s and 1980s were Closely related to the Contemporary Japanese viruses in all gene segments. These observations suggest that the Influenza C viruses Cause epidemiCs in some Communities during the same season and that antigeniCally and genetiCally similar Influenza C viruses spread throughout Japan and may be CirCulating worldwide.

Kanetsu Sugawara - One of the best experts on this subject based on the ideXlab platform.

  • EffeCt of Phosphorylation of CM2 Protein on Influenza C Virus RepliCation.
    Journal of virology, 2017
    Co-Authors: Takanari Goto, Yasushi Muraki, Kanetsu Sugawara, Yoko Matsuzaki, Yoshitaka Shimotai, Ri Sho, Seiji Hongo
    Abstract:

    CM2 is the seCond membrane protein of the Influenza C virus and has been demonstrated to play a role in the unCoating and genome paCkaging proCesses in Influenza C virus repliCation. Although the effeCts of N-linked glyCosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus repliCation have been analyzed, the effeCt of the phosphorylation of CM2 on virus repliCation remains to be determined. In this study, a phosphorylation site(s) at residue 78 and/or 103 of CM2 was replaCed with an alanine residue(s), and the effeCts of the loss of phosphorylation on Influenza C virus repliCation were analyzed. No signifiCant differenCes were observed in the paCkaging of the reporter gene between Influenza C virus-like partiCles (VLPs) produCed from 293T Cells expressing wild-type CM2 and those from the Cells expressing the CM2 mutants laCking the phosphorylation site(s). Reporter gene expression in HMV-II Cells infeCted with VLPs Containing the CM2 mutants was inhibited in Comparison with that in Cells infeCted with wild-type VLPs. The virus produCtion of the reCombinant Influenza C virus possessing CM2 mutants Containing a serine-to-alanine Change at residue 78 was signifiCantly lower than that of wild-type reCombinant Influenza C virus. Furthermore, the virus growth of the reCombinant viruses possessing CM2 with a serine-to-aspartiC aCid Change at position 78, to mimiC Constitutive phosphorylation, was virtually identiCal to that of the wild-type virus. These results suggest that phosphorylation of CM2 plays a role in effiCient virus repliCation, probably through the addition of a negative Charge to the Ser78 phosphorylation site.IMPORTANCE It is well-known that many host and viral proteins are posttranslationally modified by phosphorylation, whiCh plays a role in the funCtions of these proteins. In Influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuClear export protein (NEP), whiCh are not integrated into the membranes, affeCts the funCtions of these proteins, thereby affeCting virus repliCation. However, it was reported that phosphorylation of the Influenza A virus M2 ion Channel protein, whiCh is integrated into the membrane, has no effeCt on virus repliCation in vitro or in vivo We previously demonstrated that the Influenza C virus CM2 ion Channel protein is modified by N-glyCosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effeCts of these modifiCations, exCept phosphorylation, on virus repliCation. This is the first report demonstrating that phosphorylation of the Influenza C virus CM2 ion Channel protein, unlike that of the Influenza A virus M2 protein, plays a role in virus repliCation.

  • GenetiC Lineage and Reassortment of Influenza C Viruses CirCulating between 1947 and 2014
    Journal of virology, 2016
    Co-Authors: Yoko Matsuzaki, Kanetsu Sugawara, Seiji Hongo, Katsumi Mizuta, Yoshitaka Shimotai, Hitoshi Oshitani, Yuki Furuse, Hidekazu Nishimura
    Abstract:

    SinCe Influenza C virus was first isolated in 1947, the virus has been only oCCasionally isolated by Cell Culture; there are only four strains for whiCh Complete genome sequenCes are registered. Here, we analyzed a total of 106 Complete genomes, ranging from the first isolate from 1947 to reCent isolates from 2014, to determine the genetiC lineages of Influenza C virus, the reassortment events, and the rates of nuCleotide substitution. The results showed that there are six lineages, named C/Taylor, C/Mississippi, C/AiChi, C/Yamagata, C/Kanagawa, and C/Sao Paulo. They Contain both antigeniC and genetiC lineages of the hemagglutinin-esterase (HE) gene, and the internal genes PB2, PB1, P3, NP, M, and NS are divided into two major lineages, a C/Mississippi/80-related lineage and a C/Yamagata/81-related lineage. Reassortment events were found over the entire period of 68 years. Several outbreaks of Influenza C virus between 1990 and 2014 in Japan Consisted of reassortant viruses, suggesting that the genomiC Constellation is related to Influenza C virus epidemiCs. The nuCleotide sequenCes were highly homologous to eaCh other. The minimum perCent identity between viruses ranged from 91.1% for the HE gene to 96.1% for the M gene, and the rate of nuCleotide substitution for the HE gene was the highest, at 5.20 × 10(-4) substitutions/site/year. These results indiCate that reassortment is an important faCtor that inCreases the genetiC diversity of Influenza C virus, resulting in its ability to prevail in humans. IMPORTANCE Influenza C virus is a pathogen that Causes aCute respiratory illness in Children and results in hospitalization of infants. We previously demonstrated (Y. Matsuzaki et al., J Clin Virol 61:87-93, 2014, http://dx.doi.org/10.1016/j.jCv.2014.06.017) that periodiC epidemiCs of this virus oCCurred in Japan between 1996 and 2014 and that replaCement of the dominant antigeniC group oCCurred every several years as a result of seleCtion by herd immunity. However, the antigeniCity of the HE glyCoprotein is highly stable, and antigeniC drift has not oCCurred for at least 30 years. Here, we analyzed a total of 106 Complete genomes spanning 68 years for the first time, and we found that Influenza C viruses are CirCulating worldwide while undergoing reassortment as well as seleCtion by herd immunity, resulting in an inCreased ability to prevail in humans. The results presented in this study Contribute to the understanding of the evolution, inCluding reassortment events, underlying Influenza C virus epidemiCs.

  • IntrinsiC Temperature Sensitivity of Influenza C Virus Hemagglutinin-Esterase-Fusion Protein
    Journal of virology, 2012
    Co-Authors: Emi Takashita, Yasushi Muraki, Kanetsu Sugawara, Seiji Hongo, Hidekazu Nishimura, Hironobu Asao, Koji Suzuki, Takashi Tsuji, Yoshihiro Ohara, Yoshihiro Kawaoka
    Abstract:

    Influenza C virus repliCates more effiCiently at 33°C than at 37°C. To determine whether hemagglutinin-esterase-fusion protein (HEF), a surfaCe glyCoprotein of Influenza C virus, is a restriCting faCtor for this temperature sensitivity, we analyzed the biologiCal and bioChemiCal properties of HEF at 33°C and 37°C. We found that HEF exhibits intrinsiC temperature sensitivities for surfaCe expression and fusion aCtivity.

  • Palmitoylation of CM2 is dispensable to Influenza C virus repliCation.
    Virus research, 2011
    Co-Authors: Yasushi Muraki, Kanetsu Sugawara, Yoko Matsuzaki, Seiji Hongo, Takatoshi Furukawa, Takako Okuwa, Toshiki Himeda, Yoshiro Ohara
    Abstract:

    CM2 is the seCond membrane protein of Influenza C virus. The signifiCanCe of the posttranslational modifiCations of CM2 remains to be Clarified in the Context of viral repliCation, although the positions of the modified amino aCids on CM2 have been determined. In the present study, using reverse genetiCs we generated rCM2-C65A, a reCombinant Influenza C virus laCking CM2 palmitoylation site, in whiCh Cysteine at residue 65 of CM2 was mutated to alanine, and examined viral growth and viral protein synthesis in the reCombinant-infeCted Cells. The rCM2-C65A virus grew as effiCiently as did the parental virus in Cultured HMV-II Cells as well as in embryonated ChiCken eggs. The synthesis and bioChemiCal features of HEF, NP, M1 and mutant CM2 in the rCM2-C65A-infeCted HMV-II Cells were similar to those in the parental virus-infeCted Cells. Furthermore, membrane flotation analysis of the infeCted Cells revealed that equal amount of viral proteins was reCovered in the plasma membrane fraCtions of the rCM2-C65A-infeCted Cells to that in the parental virus-infeCted Cells. These findings indiCate that defeCt in palmitoylation of CM2 does not affeCt transport and maturation of HEF, NP and M1 as well as CM2 in virus-infeCted Cells, and palmitoylation of CM2 is dispensable to Influenza C virus repliCation.

  • Influenza C Virus NS1 Protein Upregulates the SpliCing of Viral mRNAs
    Journal of virology, 2009
    Co-Authors: Yasushi Muraki, Kanetsu Sugawara, Yoko Matsuzaki, Emi Takashita, Takatoshi Furukawa, Yoshihiko Kohno, Seiji Hongo
    Abstract:

    Pre-mRNAs of the Influenza A virus M and NS genes are poorly spliCed in virus-infeCted Cells. By Contrast, in Influenza C virus-infeCted Cells, the predominant transCript from the M gene is spliCed mRNA. The present study was performed to investigate the meChanism by whiCh Influenza C virus M gene-speCifiC mRNA (M mRNA) is readily spliCed. The ratio of M1 enCoded by a spliCed M mRNA to CM2 enCoded by an unspliCed M mRNA in Influenza C virus-infeCted Cells was about 10 times larger than that in M gene-transfeCted Cells, suggesting that a viral protein(s) other than M gene translational produCts faCilitates viral mRNA spliCing. RNase proteCtion assays showed that the spliCing of M mRNA in infeCted Cells was muCh higher than that in M gene-transfeCted Cells. The unspliCed and spliCed mRNAs of the Influenza C virus NS gene enCode two nonstruCtural (NS) proteins, NS1(C/NS1) and NS2(C/NS2), respeCtively. The introduCtion of premature translational termination into the NS gene, whiCh bloCked the synthesis of the C/NS1 and C/NS2 proteins, drastiCally reduCed the spliCing of NS mRNA, raising the possibility that C/NS1 or C/NS2 enhanCes viral mRNA spliCing. The spliCing of Influenza C virus M mRNA was inCreased by Coexpression of C/NS1, whereas it was reduCed by Coexpression of the Influenza A virus NS1 protein (A/NS1). The spliCing of Influenza A virus M mRNA was also inCreased by Coexpression of C/NS1, though it was inhibited by that of A/NS1. These results suggest that Influenza C virus NS1, but not A/NS1, Can upregulate viral mRNA spliCing.