A5078312528- Viral Infections and Outbreaks Research
- Viral gastroenteritis research and epidemiology
- Viral Infections and Vectors
- Virology and Viral Diseases
- Virus-based gene therapy research
- Hepatitis B Virus Studies
- Animal Virus Infections Studies
- Parvovirus B19 Infection Studies
- SARS-CoV-2 and COVID-19 Research
- Respiratory viral infections research
- Disaster Response and Management
- Viral Infections and Immunology Research
- HIV Research and Treatment
- Peripheral Neuropathies and Disorders
- Cytomegalovirus and herpesvirus research
- COVID-19 Clinical Research Studies
- PARP inhibition in cancer therapy
- interferon and immune responses
- Phenothiazines and Benzothiazines Synthesis and Activities
- Toxin Mechanisms and Immunotoxins
- HIV/AIDS drug development and treatment
- Fire effects on ecosystems
- Immunotherapy and Immune Responses
- Neonatal Respiratory Health Research
- Advanced Thermodynamics and Statistical Mechanics
Osaka University
1977-2025
National Center for Infectious Diseases
2022
Scripps Research Institute
2013-2020
Kyushu University
2008-2013
Université Paris-Saclay
2000
Human metapneumovirus (HMPV) is a major causative agent of severe bronchiolitis and pneumonia. Its fusion (F) protein must be cleaved by host proteases to cause membrane fusion, critical step for virus infection. By generating Vero cells constitutively expressing the transmembrane serine protease TMPRSS2 green fluorescent protein-expressing recombinant HMPV, we show that TMPRSS2, which expressed in human lung epithelium, cleaves HMPV F efficiently supports multiplication. The results...
The genome of measles virus (MV) is encapsidated by the nucleocapsid (N) protein and associates with RNA-dependent RNA polymerase to form ribonucleoprotein complex. matrix (M) believed play an important role in MV assembly linking complex envelope glycoproteins. Analyses using a yeast two-hybrid system coimmunoprecipitation mammalian cells revealed that M interacts N two leucine residues at carboxyl terminus (L523 L524) are critical for interaction. In minigenome reporter gene assays,...
Measles is an acute febrile infectious disease with high morbidity and mortality. The genome of measles virus (MV), the causative agent, encodes two accessory products, V C proteins, that play important roles in MV virulence. but not protein IC-B strain (a well-characterized virulent MV) has been shown to block Jak/Stat signaling pathway counteract cellular interferon (IFN) response. We have recently a recombinant lacks expression replicates poorly certain cell lines, its growth defect...
Lassa virus (LASV) infects several hundred thousand people in Western Africa, resulting many lethal fever (LF) cases. Licensed LF vaccines are not available, and anti-LF therapy is limited to off-label use of the nucleoside analog ribavirin with uncertain efficacy. We describe generation a novel live-attenuated LASV vaccine candidate. This candidate based on mutating wild-type (WT) key region viral genome, glycoprotein precursor (GPC) gene. These mutations do change encoded GPC but interfere...
Several arenaviruses, chiefly Lassa virus (LASV), cause hemorrhagic fever (HF) disease in humans and pose a great public health concern the regions which they are endemic. Moreover, evidence indicates that worldwide-distributed prototypic arenavirus lymphocytic choriomeningitis (LCMV) is neglected human pathogen of clinical significance. The limited existing armamentarium to combat human-pathogenic arenaviruses underscores importance developing novel antiarenaviral drugs, task would be...
ABSTRACT Many viruses use the host trafficking system at a variety of their replication steps. Measles virus (MV) possesses nonsegmented negative-strand RNA genome that encodes three components ribonucleoprotein (RNP) complex (N, P, and L), two surface glycoproteins, matrix protein, nonstructural proteins. A subset immune cells polarized epithelial are in vivo targets MV, MV is selectively released from apical membrane cells. However, molecular mechanisms for release remain largely unknown....
Several mammalian arenaviruses (mammarenaviruses) cause hemorrhagic fevers in humans and pose serious public health concerns their endemic regions. Additionally, mounting evidence indicates that the worldwide-distributed, prototypic mammarenavirus, lymphocytic choriomeningitis virus (LCMV), is a neglected human pathogen of clinical significance. Concerns about human-pathogenic mammarenaviruses are exacerbated by lack licensed vaccines, current anti-mammarenavirus therapy limited to off-label...
ABSTRACT Several arenaviruses cause hemorrhagic fever disease in humans and represent important public health problems the regions where these viruses are endemic. In addition, evidence indicates that worldwide-distributed prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is an neglected human pathogen. There no licensed vaccines current antiarenavirus therapy limited to use of ribavirin only partially effective. Therefore, there unmet need for novel antiarenaviral...
Lassa virus (LASV), a mammarenavirus, infects an estimated 100,000⁻300,000 individuals yearly in western Africa and frequently causes lethal disease. Currently, no LASV-specific antivirals or vaccines are commercially available for prevention treatment of fever, the disease caused by LASV. The development medical countermeasure screening platforms is crucial step to yield licensable products. Using reverse genetics, we generated recombinant wild-type LASV (rLASV-WT) modified version thereof...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of disease 2019 (COVID-19), employs host-cell angiotensin-converting enzyme (ACE2) for cell entry. Genetic analyses ACE2 have identified several single-nucleotide polymorphisms (SNPs) specific to different human populations. Molecular dynamics simulations indicated that these SNPs could affect interactions between SARS-CoV-2 and ACE2, thereby providing a partial explanation regional differences observed in...
ABSTRACT Most viruses possess strategies to circumvent host immune responses. The measles virus (MV) nonstructural C protein suppresses the interferon response, thereby allowing efficient viral growth, but its detailed mechanism has been unknown. We identified Shc Src homology 2 domain-binding 1 (SHCBP1) as one of proteins interacting with protein. Knockdown SHCBP1 using a short-hairpin RNA greatly reduced MV growth. was found be required for synthesis in minigenome assay and bind...
ABSTRACT Hemorrhagic fever arenaviruses (HFA) pose important public health problems in regions where they are endemic. Thus, Lassa virus (LASV) infects several hundred thousand individuals yearly West Africa, causing a large number of cases associated with high morbidity and mortality. Concerns about human-pathogenic exacerbated because the lack FDA-licensed arenavirus vaccines current antiarenaviral therapy is limited to an off-label use ribavirin that only partially effective. The Mopeia...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters cells using angiotensin-converting enzyme (ACE2) and neuropilin-1 (NRP-1) as the primary receptor entry co-factor, respectively. Cell is first major step in initiation of viral life cycle, representing an ideal target for antiviral interventions. In this study, we used a recombinant replication-deficient vesicular stomatitis virus-based pseudovirus bearing spike protein SARS-CoV-2 (SARS2-S) to screen US Food Drug...
Lassa virus (LASV), the causative agent of fever, infects several hundred thousand people in Western Africa, resulting many lethal fever cases. No U.S. Food and Drug Administration-licensed countermeasures are available to prevent or treat LASV infection. We describe generation a novel live-attenuated vaccine candidate rLASV(IGR/S-S), which is based on replacement large genomic segment noncoding intergenic region (IGR) with that small genome segment. rLASV(IGR/S-S) less fit cell culture than...
ABSTRACT Hemorrhagic fever arenaviruses (HFAs) pose important public health problems in regions where they are endemic. Concerns about human-pathogenic exacerbated because of the lack FDA-licensed arenavirus vaccines and current antiarenaviral therapy is limited to an off-label use ribavirin that only partially effective. We have recently shown noncoding intergenic region (IGR) present each genome segment, S L segments (S-IGR L-IGR, respectively), plays roles control virus protein expression...
Measles virus (MV), a human pathogen, uses the signaling lymphocyte activation molecule (SLAM) or CD46 as an entry receptor. Although several transgenic mice expressing these receptors have been generated small animal models for measles, usually to be made defective in IFN-α/β facilitate MV replication. Similarly, when functional are expressed by transfection, mouse cells do not allow growth efficiently primate cells. In this study, we demonstrate that grows SLAM-expressing which Sendai...
Mammalian arenavirus (mammarenavirus) mRNAs are characterized by 5'-capped and 3'-nonpolyadenylated untranslated regions (UTRs). We previously reported that the nonpolyadenylated 3'-UTR of viral mRNA (vmRNA), which is derived from noncoding intergenic region (IGR), regulates protein levels at posttranscriptional level. This finding provided basis for development novel live-attenuated vaccines (LAVs) against human pathogenic mammarenaviruses. Detailed information about roles specific vmRNA...
Mammarenaviruses cause chronic infections in their natural rodent hosts. Infected rodents shed infectious virus into excreta. Humans are infected through mucosal exposure to aerosols or direct contact of abraded skin with fomites, resulting a wide range manifestations from asymptomatic mild febrile illness severe life-threatening hemorrhagic fever. The mammarenavirus matrix Z protein has been shown be main driving force budding and act as negative regulator viral RNA synthesis. To gain...
In this study, we document that efficient interaction between arenavirus nucleoprotein (NP) and RNA-dependent RNA polymerase (L protein), the two trans-acting viral factors required for both virus replication gene transcription, requires presence of virus-specific sequences located within untranslated 5' 3' termini genome.
The P, V, and C proteins of measles virus are encoded in overlapping reading frames the P gene, which makes it difficult to analyze functions individual context infection. We established a system protein independently from V by placing its gene an additional transcription unit between H L genes. Analyses with this indicated that highly attenuated Edmonston lineage vaccine strain encodes fully functional protein, and/or is involved phenotype.
Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV). mainly prevalent in East Asia. It has a mortality rate of up to 30%, and there no approved treatment against disease. In this study, we evaluated effect loperamide, antidiarrheal antihyperalgesic agent, on propagation SFTSV cell culture system. Methods: SFTSV-infected human lines were exposed viral titers evaluated. To clarify mode action several...
Several arenaviruses, chiefly Lassa virus (LASV), cause hemorrhagic fever disease in humans and pose serious public health concerns their regions of endemicity. Moreover, mounting evidence indicates that the worldwide-distributed prototypic arenavirus, lymphocytic choriomeningitis (LCMV), is a neglected human pathogen clinical significance. We have documented recombinant LCMV containing glycoprotein (GPC) gene LASV within backbone immunosuppressive clone 13 (Cl-13) variant Armstrong strain...