Asthma, an allergic disease of the airways, is a risk factor for severity of common respiratory viral infections; however, the relationship between asthma and severity in COVID-19 remains unclear. Here, we examined the effects of SARS-CoV-2 (Omicron BA.5 strain) infection in a mouse model of airway allergy. First, stimulation of allergic mice with OVA resulted in the appearance of ACE2-negative mucus-secreting goblet cells in the bronchiolar region, and an increase in the number of ACE2-expressing cells in the alveoli. As a result, ACE2-expressing cells, which are susceptible to SARS-CoV-2, were limited to the distal portion of the bronchioles while they increased in the alveolar area. After viral infection, the peak infectious viral load in the OVA group was 100-fold lower than that in the phosphate buffered saline (PBS) group; however, clearance of viral RNA from the upper/lower airways was delayed. There were notable differences in acquisition of nsp5 and nsp6 mutations by the Omicron BA.5 strain recovered from BALF samples obtained from the OVA and PBS groups. Immune responses associated with viral clearance were essentially the same, but expression of granulocyte-associated chemokines was higher, M2 macrophage responses were predominant, and the higher spike-specific IgG1/IgG2a ratio in the OVA group post-infection. Infection localized in the alveolar region earlier in the OVA group, resulting in more severe alveolar damage than in the PBS group. These data suggest a Th2-shifted immune background and altered localization of SARS-CoV-2 susceptible cells in mice with OVA-induced airway allergy, which reflect Omicron BA.5 infection dynamics, viral mutations, and immunopathology.
{"title":"A Mouse Model of Ovalbumin-Induced Airway Allergy Exhibits Altered Localization of SARS-CoV-2-Susceptible Cells in the Lungs, Which Reflects Omicron BA.5 Infection Dynamics, Viral Mutations, and Immunopathology.","authors":"Takao Iketani, Kaya Miyazaki, Naoko Iwata-Yoshikawa, Yusuke Sakai, Nozomi Shiwa-Sudo, Seiya Ozono, Hideki Asanuma, Hideki Hasegawa, Tadaki Suzuki, Noriyo Nagata","doi":"10.1111/1348-0421.13184","DOIUrl":"https://doi.org/10.1111/1348-0421.13184","url":null,"abstract":"<p><p>Asthma, an allergic disease of the airways, is a risk factor for severity of common respiratory viral infections; however, the relationship between asthma and severity in COVID-19 remains unclear. Here, we examined the effects of SARS-CoV-2 (Omicron BA.5 strain) infection in a mouse model of airway allergy. First, stimulation of allergic mice with OVA resulted in the appearance of ACE2-negative mucus-secreting goblet cells in the bronchiolar region, and an increase in the number of ACE2-expressing cells in the alveoli. As a result, ACE2-expressing cells, which are susceptible to SARS-CoV-2, were limited to the distal portion of the bronchioles while they increased in the alveolar area. After viral infection, the peak infectious viral load in the OVA group was 100-fold lower than that in the phosphate buffered saline (PBS) group; however, clearance of viral RNA from the upper/lower airways was delayed. There were notable differences in acquisition of nsp5 and nsp6 mutations by the Omicron BA.5 strain recovered from BALF samples obtained from the OVA and PBS groups. Immune responses associated with viral clearance were essentially the same, but expression of granulocyte-associated chemokines was higher, M2 macrophage responses were predominant, and the higher spike-specific IgG1/IgG2a ratio in the OVA group post-infection. Infection localized in the alveolar region earlier in the OVA group, resulting in more severe alveolar damage than in the PBS group. These data suggest a Th2-shifted immune background and altered localization of SARS-CoV-2 susceptible cells in mice with OVA-induced airway allergy, which reflect Omicron BA.5 infection dynamics, viral mutations, and immunopathology.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bacterial reverse transcriptase coding gene (RT) is essential for the production of a small satellite DNA-RNA complex called multicopy single-stranded DNA (msDNA). In this study, we found a novel retron, retron-Vmi1 (Vm85) from Vibrio mimicus. The retron is comprised of the msr-msd region, orf323, and the ret gene, a genetic organization similar to Salmonella's retron-Sen2 (St85). The protein sequence of the RNA-directed DNA polymerase (RT-Vmi1) is highly homologous to the RTs of Vibrio metoecus, Vibrio parahaemolyticus, and Vibrio vulnificus. Phylogenetic and protein sequence similarity analysis of retron-Vmi1 ORF323 and RT revealed a close relatedness to retron-Sen2. We found that retron-Vmi1 was inserted in the dusA gene, similar to the insertion of the retron-Vpa1 (Vp96) of V. parahaemolyticus AQ3354, suggesting that retrons can be transferred via the tRNA gene. These results are the first convincing evidence that retron is moving across species. The neighboring genes of retron-Vmi1 shared high homology with the genetic environment of V. parahaemolyticus and V. vulnificus retrons. We also found two junction points within the retron-Vmi1 and the dusA gene suggesting that retron-Vmi1 was inserted into this site in a two-step manner.
{"title":"Genetic Characterization of a Novel Retron Element Isolated from Vibrio mimicus.","authors":"Jant Cres Caigoy, Toshi Shimamoto, Yojiro Ishida, Ashraf M Ahmed, Shin-Ichi Miyoshi, Tadashi Shimamoto","doi":"10.1111/1348-0421.13181","DOIUrl":"10.1111/1348-0421.13181","url":null,"abstract":"<p><p>Bacterial reverse transcriptase coding gene (RT) is essential for the production of a small satellite DNA-RNA complex called multicopy single-stranded DNA (msDNA). In this study, we found a novel retron, retron-Vmi1 (Vm85) from Vibrio mimicus. The retron is comprised of the msr-msd region, orf323, and the ret gene, a genetic organization similar to Salmonella's retron-Sen2 (St85). The protein sequence of the RNA-directed DNA polymerase (RT-Vmi1) is highly homologous to the RTs of Vibrio metoecus, Vibrio parahaemolyticus, and Vibrio vulnificus. Phylogenetic and protein sequence similarity analysis of retron-Vmi1 ORF323 and RT revealed a close relatedness to retron-Sen2. We found that retron-Vmi1 was inserted in the dusA gene, similar to the insertion of the retron-Vpa1 (Vp96) of V. parahaemolyticus AQ3354, suggesting that retrons can be transferred via the tRNA gene. These results are the first convincing evidence that retron is moving across species. The neighboring genes of retron-Vmi1 shared high homology with the genetic environment of V. parahaemolyticus and V. vulnificus retrons. We also found two junction points within the retron-Vmi1 and the dusA gene suggesting that retron-Vmi1 was inserted into this site in a two-step manner.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sakika Kimura, Hidehiko Suzuki, Yu Hatakeyama, Takafumi Noguchi, Koga Ii, Kazumasa Nakamura, Hirotaka Ebina, Eiji Morita
Human parvovirus B19 (B19V) causes fetal hydrops in pregnant women. Despite the significant impact of this virus, effective vaccines remain unclear. In this study, we successfully engineered B19V protein nanoparticles by fusing the N-terminal receptor-binding domain corresponding to 5-80 amino acids of VP1 with two distinct types of self-assembling protein nanoparticles. Gel filtration and electron microscopic analysis confirmed the spherical assembly of the antigen-fused nanoparticles. The purified nanoparticles are efficiently bound to the surface of UT7/Epo-S1 cells, which are semi-permissive hosts for B19V infection. Immunization of BALB/c mice with VP1u 5-80 nanoparticles elicited a robust production of B19V-specific IgG antibodies compared to single VP1u 5-80 peptides. Moreover, a neutralization assay using B19V derived from a blood donor sample revealed that antibodies from mice immunized with VP1u 5-80 nanoparticles exhibited stronger infection-neutralizing activity. These findings suggest that nanoparticle formation plays a crucial role in enhancing the immunogenicity of the B19V VP1u 5-80 amino acid peptide and that these nanoparticles could serve as promising vaccine candidates, effectively inducing immunity against B19V.
{"title":"Efficient Neutralizing Antibodies Induction by Human Parvovirus B19 Epitope-Presenting Protein Nanoparticles.","authors":"Sakika Kimura, Hidehiko Suzuki, Yu Hatakeyama, Takafumi Noguchi, Koga Ii, Kazumasa Nakamura, Hirotaka Ebina, Eiji Morita","doi":"10.1111/1348-0421.13182","DOIUrl":"10.1111/1348-0421.13182","url":null,"abstract":"<p><p>Human parvovirus B19 (B19V) causes fetal hydrops in pregnant women. Despite the significant impact of this virus, effective vaccines remain unclear. In this study, we successfully engineered B19V protein nanoparticles by fusing the N-terminal receptor-binding domain corresponding to 5-80 amino acids of VP1 with two distinct types of self-assembling protein nanoparticles. Gel filtration and electron microscopic analysis confirmed the spherical assembly of the antigen-fused nanoparticles. The purified nanoparticles are efficiently bound to the surface of UT7/Epo-S1 cells, which are semi-permissive hosts for B19V infection. Immunization of BALB/c mice with VP1u 5-80 nanoparticles elicited a robust production of B19V-specific IgG antibodies compared to single VP1u 5-80 peptides. Moreover, a neutralization assay using B19V derived from a blood donor sample revealed that antibodies from mice immunized with VP1u 5-80 nanoparticles exhibited stronger infection-neutralizing activity. These findings suggest that nanoparticle formation plays a crucial role in enhancing the immunogenicity of the B19V VP1u 5-80 amino acid peptide and that these nanoparticles could serve as promising vaccine candidates, effectively inducing immunity against B19V.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bovine spongiform encephalopathy (BSE) is a prion disease in cattle caused by classical-type (C-), L-type (L-), or H-type (H-) BSE prions. While C-BSE prions are zoonotic agents responsible for variant Creutzfeldt-Jakob disease, L- and H-BSE prions are believed not to be connected to human prion diseases. However, L-BSE prions have been shown to transmit to cynomolgus monkeys (Macaca fascicularis), suggesting they may have zoonotic potential. In the present study, we examined whether H-BSE prions are transmissible to cynomolgus monkeys. The monkeys were injected intracranially (n = 2) or given orally (n = 2) with brain homogenates from a cow infected with H-BSE prions. After asymptomatic observation periods of 4-6 years, the monkeys were euthanized for autopsy. Histological examination of the brain did not reveal any pathological changes. Immunohistochemical and Western blot analyses did not detect disease-associated forms of prion protein (PrPSc) in the brain, peripheral neurons, or lymphatic tissues. The unsuccessful transmission indicates an effective barrier against the transmission of cattle H-BSE prions to cynomolgus monkeys. Based on the results obtained in this nonhuman primate model, we estimated that the potential transmission of H-BSE prions to humans is substantially lower than C- and L-BSE prions.
{"title":"Lack of Evidence for Transmission of Atypical H-Type Bovine Spongiform Encephalopathy Prions (H-BSE Prions) by Intracranial and Oral Challenges to Nonhuman Primates.","authors":"Hiroaki Shibata, Fumiko Ono, Yuko Sato, Keiko Ohto, Nozomi Nakano, Morikazu Imamura, Motohiro Horiuchi, Minoru Tobiume, Ken'ichi Hagiwara","doi":"10.1111/1348-0421.13180","DOIUrl":"https://doi.org/10.1111/1348-0421.13180","url":null,"abstract":"<p><p>Bovine spongiform encephalopathy (BSE) is a prion disease in cattle caused by classical-type (C-), L-type (L-), or H-type (H-) BSE prions. While C-BSE prions are zoonotic agents responsible for variant Creutzfeldt-Jakob disease, L- and H-BSE prions are believed not to be connected to human prion diseases. However, L-BSE prions have been shown to transmit to cynomolgus monkeys (Macaca fascicularis), suggesting they may have zoonotic potential. In the present study, we examined whether H-BSE prions are transmissible to cynomolgus monkeys. The monkeys were injected intracranially (n = 2) or given orally (n = 2) with brain homogenates from a cow infected with H-BSE prions. After asymptomatic observation periods of 4-6 years, the monkeys were euthanized for autopsy. Histological examination of the brain did not reveal any pathological changes. Immunohistochemical and Western blot analyses did not detect disease-associated forms of prion protein (PrP<sup>Sc</sup>) in the brain, peripheral neurons, or lymphatic tissues. The unsuccessful transmission indicates an effective barrier against the transmission of cattle H-BSE prions to cynomolgus monkeys. Based on the results obtained in this nonhuman primate model, we estimated that the potential transmission of H-BSE prions to humans is substantially lower than C- and L-BSE prions.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
It has been reported that the high-growth reassortant (HGR) A(H3N2) influenza viruses used for split influenza vaccine (SV) production have some amino acid substitutions in hemagglutinin due to egg adaptation during virus propagation, causing antigenic differences between HGR and epidemic viruses. To clarify whether inactivated whole-virus vaccine (WV) derived from the A(H3N2) HGR virus possessing egg adaptation could induce cross-protective immune responses against epidemic A(H3N2) viruses, the efficacy of WV was compared with that of SV in a ferret model. When the ferrets immunized with WV or SV derived from HGR A/Victoria/361/2011 (IVR-165) virus were challenged with the homologous virus A/Victoria/361/2011 (IVR-165) or its original cell-propagated A/Victoria/361/2011 virus, respectively, WV successfully shortened the duration of virus shedding of both challenge viruses, whereas SV shortened only that of the homologous virus, A/Victoria/361/2011 (IVR-165). When WV-immunized ferrets were challenged with A/Fukushima/69/2015 virus, which is an epidemic virus antigenically different from the A/Victoria/361/2011 virus, WV could shorten the duration of shedding of this virus. In addition, we found that early induction of nasal IgG and IgA antibodies by vaccines helped shorten the virus-shedding period, although this was dependent on the degree of difference in antigenicity of the challenge virus. These results indicate that vaccination with WV, not with SV, would be a solution to avoid decreased vaccine effectiveness due to the antigenic change of HGR virus by egg adaptation during virus propagation.
{"title":"Efficacy of an Inactivated Whole-Virus A/Victoria/361/2011 (IVR-165) (H3N2) Influenza Vaccine in Ferrets.","authors":"Noriko Kishida, Masaki Imai, Akira Ainai, Hideki Asanuma, Reiko Saito, Seiichiro Fujisaki, Masayuki Shirakura, Kazuya Nakamura, Tomoko Kuwahara, Emi Takashita, Masato Tashiro, Takato Odagiri, Shinji Watanabe","doi":"10.1111/1348-0421.13179","DOIUrl":"https://doi.org/10.1111/1348-0421.13179","url":null,"abstract":"<p><p>It has been reported that the high-growth reassortant (HGR) A(H3N2) influenza viruses used for split influenza vaccine (SV) production have some amino acid substitutions in hemagglutinin due to egg adaptation during virus propagation, causing antigenic differences between HGR and epidemic viruses. To clarify whether inactivated whole-virus vaccine (WV) derived from the A(H3N2) HGR virus possessing egg adaptation could induce cross-protective immune responses against epidemic A(H3N2) viruses, the efficacy of WV was compared with that of SV in a ferret model. When the ferrets immunized with WV or SV derived from HGR A/Victoria/361/2011 (IVR-165) virus were challenged with the homologous virus A/Victoria/361/2011 (IVR-165) or its original cell-propagated A/Victoria/361/2011 virus, respectively, WV successfully shortened the duration of virus shedding of both challenge viruses, whereas SV shortened only that of the homologous virus, A/Victoria/361/2011 (IVR-165). When WV-immunized ferrets were challenged with A/Fukushima/69/2015 virus, which is an epidemic virus antigenically different from the A/Victoria/361/2011 virus, WV could shorten the duration of shedding of this virus. In addition, we found that early induction of nasal IgG and IgA antibodies by vaccines helped shorten the virus-shedding period, although this was dependent on the degree of difference in antigenicity of the challenge virus. These results indicate that vaccination with WV, not with SV, would be a solution to avoid decreased vaccine effectiveness due to the antigenic change of HGR virus by egg adaptation during virus propagation.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}