IFN-γ derived from activated human CD4 T cells inhibits the replication of SARS-CoV-2 depending on cell-type and viral strain.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination elicit both T cell and B cell immune responses in immunocompetent individuals. However, the mechanisms underlying the antiviral effects mediated by CD4 T cells are not fully understood. In this study, we analyzed the culture supernatant (SN) from polyclonally stimulated human CD4 T cells as a model for soluble mediators derived from SARS-CoV-2-stimulated CD4 T cells.

iPS cell-derived model to study the interaction between tissue macrophage and HIV-1.

Despite effective antiretroviral therapy, HIV-1 persists in cells, including macrophages, which is an obstacle to cure. However, the precise role of macrophages in HIV-1 infection remains unclear because they reside in tissues that are not easily accessible. Monocyte-derived macrophages are widely used as a model in which peripheral blood monocytes are cultured and differentiated into macrophages.

Development of a rapid assay system for detecting antibody-dependent enhancement of dengue virus infection.

Antibody-dependent enhancement (ADE) is one of the pathogenic mechanisms related to disease severity in dengue virus infection. Conventional assays for detecting ADE activity usually require several days. In this study, we established a rapid assay system to evaluate ADE activity in dengue-seropositive samples using single round infectious particles (SRIPs).

Reevaluation of antibody-dependent enhancement of infection in anti-SARS-CoV-2 therapeutic antibodies and mRNA-vaccine antisera using FcR- and ACE2-positive cells.

Many therapeutic antibodies (Abs) and mRNA vaccines, both targeting SARS-CoV-2 spike protein (S-protein), have been developed and approved in order to combat the ongoing COVID-19 pandemic. In consideration of these developments, a common concern has been the potential for Ab-dependent enhancement (ADE) of infection caused by inoculated or induced Abs. Although the preventive and therapeutic effects of these Abs are obvious, little attention has been paid to the influence of the remaining and dwindling anti-S-protein Abs in vivo.

The potential of COVID-19 patients' sera to cause antibody-dependent enhancement of infection and IL-6 production.

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many vaccine trials have been initiated. An important goal of vaccination is the development of neutralizing antibody (Ab) against SARS-CoV-2. However, the possible induction of antibody-dependent enhancement (ADE) of infection, which is known for other coronaviruses and dengue virus infections, is a particular concern in vaccine development.

Dengue virus susceptibility in novel immortalized myeloid cells.

Human dendritic cells (DCs) are the main target cells of dengue virus (DENV). Because humans injected with even a small volume of DENV from mosquito saliva display a high level of viremia, DCs are expected to be highly susceptible to DENV. In the present study, we assessed the efficiency of DENV infection using the novel immortalized human myeloid cell lines iPS-ML and iPS-DC.

Design, synthesis, and optimization of a series of 2-azaspiro[3.3]heptane derivatives as orally bioavailable fetal hemoglobin inducers.

Pharmacological reactivation of the γ-globin gene for the production of fetal hemoglobin (HbF) is a promising approach for the management of β-thalassemia and sickle cell disease (SCD). We conducted a phenotypic screen in human erythroid progenitor cells to identify molecules that could induce HbF, which resulted in identification of the hit compound 1. Exploration of structure-activity relationships and optimization of ADME properties led to 2-azaspiro[3.

Phenotypic-screening generates active novel fetal globin-inducers that downregulate Bcl11a in a monkey model.

Heritable disorders associated with hemoglobin production are the most common monogenic disorders. These are mainly represented by disorders such as β-thalassemia and sickle cell disease. Induction of fetal hemoglobin (HbF) has been known to ameliorate the clinical severity of these β hemoglobinopathies.

Discovery and in vivo effects of novel human natriuretic peptide receptor A (NPR-A) agonists with improved activity for rat NPR-A.

Natriuretic peptide receptor A (NPR-A) agonists were evaluated in vivo by optimizing the structure of quinazoline derivatives to improve agonistic activity for rat NPR-A. A 1,4-Cis-aminocyclohexylurea moiety at 4-position and hydroxy group of d-alaninol at 2-position on the quinazoline ring were found to be important factors in improving rat NPR-A activity. We identified potent quinazoline and pyrido[2,3-d]pyrimidine derivatives against rat NPR-A, with double-digit nanomolar EC values.

Simultaneous detection and genogroup-screening test for norovirus genogroups I and II from fecal specimens in single tube by reverse transcription- loop-mediated isothermal amplification assay.

We developed a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay for the rapid detection of noroviruses (NoVs) in a genogroup-specific manner in a previous study. In this study, to detect NoVs more easily and simply, we have developed an RT-LAMP assay for the simultaneous detection of NoV genogroup I (GI) and II (GII) genomes in a single tube. The genogrouping was achieved by using fluorescence-labeled primers, and the green and red colors for GI and GII, respectively, sometimes with yellow color for GI and GII mixture, were indicated on the agarose gel under UV light at 312 nm.

[Evaluation of immunochromatography test for rapid detection of influenza A and B viruses using real-time PCR].

The sensitivity of rapid diagnostic kits to influenza B is lower than to influenza A. The cause-poor performance of the kit or the scarcity of viruses in type B specimens-has yet to be clarified. Using real-time PCR, we measured the amount of influenza viruses with nasopharyngeal aspirate fluid previously identified by virus isolation culture and passing the rapid diagnosis test by four types of kits, including the ESPLINE Influenza A&B-N (Fujirebio Corp.

Rapid detection of norovirus from fecal specimens by real-time reverse transcription-loop-mediated isothermal amplification assay.

In this study, we developed a one-step, single-tube genogroup-specific reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay for the detection of norovirus (NoV) genomes targeting from the C terminus of the RNA-dependent RNA polymerase gene to the capsid N-terminal/shell domain region. This is the first report on the development of an RT-LAMP assay for the detection of NoV genomes. Because of the diversity of NoV genotypes, we used 9 and 13 specially designed primers containing mixed bases for genogroup I (GI) and II (GII), respectively.

[Eleven cases of co-infection with influenza type A and type B suspected by use of a rapid diagnostic kit and confirmed by RT-PCR and virus isolation].

In the 2004/05 influenza season there were epidemics of influenza caused by several types of viruses (type B and A (H3) viruses, and type B, A (H3), and A (H1) viruses) in many areas of Japan. In such epidemics a single individual could be co-infected with several influenza viruses. From February to March in 2005, we examined 15 patients who were positive for influenza type A and B viruses when tested with a rapid diagnostic kit.

Japanese encephalitis virus in meningitis patients, Japan.

Cerebrospinal fluid specimens from 57 patients diagnosed with meningitis were tested for Japanese encephalitis virus. Total RNA was extracted from the specimens and amplified. Two products had highest homology with Nakayama strain and 2 with Ishikawa strain.

[The clinical features about 5 cases of Japanese encephalitis reported in Japan, 2002].

We discussed the clinical features of 5 Japanese encephalitis (JE) cases which we experienced in 2002. Today there are few opportunities for a clinician to see JE patients. Until the 1950s, the number of JE patients was more than 2000 in Japan, but the annual cases of JE are decreasing remarkably due to the extermination of mosquitoes, thorough vaccination and improvement of environmental sanitation.

[Incidence and prevalent types of Norwalk virus, Sapporo virus and human astrovirus in pediatric gastroenteritis in Hiroshima Prefecture].

The incidence and prevalent types of Norwalk virus (NV), Sapporo virus (SV), and human astrovirus (HAstV) in pediatric gastroenteritis in Hiroshima Prefecture were investigated in 7 cold seasons, between 1995/96 and 2001/02. The incidences of NV, SV, and HAstV were 23.6% ranging from 16.

An application of microplate hybridization assay for the confirmation and probe typing of "Norwalk-like viruses".

"Norwalk-like virus" (NLV) genomes are generally detected by using reverse transcription-PCR and confirmed by blot hybridization and nucleotide sequencing because of their fastidious nature. In the present study, the confirmation and typing of NLV genomes were carried out using a streptavidin-biotin binding technique and microplate hybridization assay with digoxigenin labeled probes. Eight probe typing sets (G1A, G1B, G2A, G2B, G2C, G2D, G2E, and G2F) formatted from 6 newly designed probes and 8 probes reported elsewhere were used for hybridization.