The Role of IL-4+ Memory T Cells in SARS-CoV-2 Booster Vaccination.

Vaccines effectively stimulate protective immune responses in healthy individuals, but the precise roles of germinal center (GC) and follicular helper T (TFH) cells in SARS-CoV-2 vaccine responses are not fully understood. This study used a conditional loss-of-function mouse model to investigate antibody responses to the Wuhan spike protein, specifically eliminating newly developed TFH cells during either the primary or memory phase. Our findings demonstrated that TFH-mediated GC responses are essential for primary vaccination.

Strengthening Bilateral Cooperation Through the Japanese Ministry of Health, Labour, and Welfare Liaison to the US Administration for Strategic Preparedness and Response.

Beginning in 2016, the Japanese Ministry of Health, Labour and Welfare (MHLW) began stationing liaisons within the US Department of Health and Human Services (HHS) Administration for Strategic Preparedness and Response to strengthen cooperation on bilateral health security engagement and collaboration. Notable accomplishments include the establishment of the US-Japan Health Security Committee and collaborations between the US-Japan Disaster Medical Assistance Team on mass event responses, such as the repatriation of American citizens from the Diamond Princess in February 2020 and the COVID-19 response. Japan has also embedded liaisons at the US Centers for Disease Control and Prevention to advance collaboration on public health.

What drives respondents to seroepidemiological surveys? Insights from COVID-19 and implications for future pandemics.

Background: Non-random participation can undermine the representativeness of seroepidemiological surveys. Despite their critical role in estimating disease spread during pandemics, non-response bias and methods to correct it require further investigation. This study aimed to examine sociodemographic characteristics and COVID-19-related factors influencing participation in a seroepidemiological survey.

Human Leukocyte Antigen Genotypes Affect Hepatitis B Virus Mutations Associated With Hepatocellular Carcinoma.

Background And Aims: Various viral mutations have been reported to influence disease pathogenesis in infectious diseases. However, these mutations may remain undetected due to patient population changes. Although many causes have been proposed, the exact reasons remain unclear.

Synergistic activation of bat SARS-like coronaviruses spike protein by elastase and TMPRSS2.

Although numerous sarbecoviruses have been identified in bats, but most lack the ability to infect human cells. Some barriers limit coronavirus zoonosis, including susceptibility to host proteases. Here, we investigated whether exogenous protease treatment can circumvent host restrictions in two severe acute respiratory syndrome (SARS)-related bat coronaviruses.

miRNA-29b-1-5p mediates an antiviral activity by targeting the HBV entry receptor in human hepatocytes.

Chronic hepatitis B virus (HBV) infections represent a major global health burden requiring effective therapeutic interventions. This study investigates the antiviral potential of microRNAs (miRNAs) targeting the HBV entry receptor, sodium-taurocholate cotransporting polypeptide (NTCP). Using an experimental model of primary human hepatocytes (PHHs), we highlighted a set of candidate antiviral miRNAs induced by interferon (IFN) alpha analog treatment.

RXR agonist S169 inhibits HBV/HDV entry in vitro by disrupting KIF4-dependent NTCP trafficking.

Chronic hepatitis B (HBV) and hepatitis D (HDV) viral infections pose serious global health challenges, and the lack of curative therapies calls for the development of new antiviral approaches. Recently, we have identified the Kinesin Family Member 4 (KIF4) as a crucial regulator of the surface transport for NTCP (HBV/HDV entry receptor). Our research has shown that the pan-RXR agonist, Bexarotene, suppresses KIF4 expression and inhibits HBV/HDV infections.

Molecular mechanisms of hepatitis B virus entry inhibition by a bile acid derivative INT-767 binding to the preS1 region.

Hepatitis B virus (HBV) infection is a leading cause of liver disease worldwide, necessitating the development of novel antiviral agents targeting various steps in the HBV life cycle. The HBV preS1 region mediates critical steps in viral entry, including binding to sodium taurocholate co-transporting polypeptide (NTCP), making it a potential target for anti-HBV drug development. Our previous study suggested that the bile acid derivative INT-767 preferentially attaches to preS1 rather than to NTCP on hepatocytes, indicating that HBV infection is inhibited by INT-767 binding to an important domain of preS1.

Serum anti-nucleocapsid antibody correlates of protection from SARS-CoV-2 re-infection regardless of symptoms or immune history.

Background: High spike-based vaccine coverage led to a high seroprevalence of anti-spike (S) antibodies against SARS-CoV-2 in Japanese adults in 2024. Nevertheless, the COVID-19 epidemic continues, and individuals with hybrid immunity are becoming more common in these populations.

Methods: We conducted a prospective cohort study to measure serum anti-SARS-CoV-2 antibody levels in 4496 Japanese adults as part of the national seroepidemiological survey.

Enhancing health security against infectious diseases: Perspectives on the emergency operations capabilities of the Japan Institute for Health Security.

The Japan Institute for Health Security (JIHS) will be established in April 2025 by merging the National Institute of Infectious Diseases (NIID) and the National Center for Global Health and Medicine (NCGM). JIHS aims to enhance health security against infectious disease crises by integrating NIID's surveillance, epidemiologic investigation, and research expertise with NCGM's clinical care and research capabilities. An effective response to an infectious disease crisis depends on robust intelligence, systematic data analysis, and surge capacity - the ability to rapidly scale responses through mobilization of resources and an established infrastructure.

The establishment of the Japan Institute for Health Security (JIHS): A new era in infectious disease response and research.

On April 1, 2025, the National Center for Global Health and Medicine (NCGM) and the National Institute of Infectious Diseases (NIID) will be merged to establish the Japan Institute for Health Security (JIHS). This merger strengthens Japan's capacity to address infectious diseases and health threats, aiming for a resilient and secure society. This paper highlights the establishment of JIHS, its alignment with government reforms, and its strategic priorities for the future.

MicroRNA-3145 as a potential therapeutic target for hepatitis B virus: inhibition of viral replication via downregulation of HBS and HBX.

Current treatments for hepatitis B virus (HBV), such as interferons and nucleic acid analogs, have limitations due to side effects like depression and the development of drug-resistant mutants, highlighting the need for new therapeutic approaches. In this study, we identified microRNA-3145 (miR-3145) as a host-derived miRNA with antiviral activity that is upregulated in primary hepatocytes during HBV infection. The expression of its precursor, pri-miR-3145, increased in response to the the virus infection, and miR-3145 downregulated the hepatitis B virus S (HBS) antigen and hepatitis B virus X (HBX), thereby inhibiting viral replication.

Prediction of cccDNA dynamics in hepatitis B patients by a combination of serum surrogate markers.

Quantification of intrahepatic covalently closed circular DNA (cccDNA) is a key for evaluating an elimination of hepatitis B virus (HBV) in infected patients. However, quantifying cccDNA requires invasive methods such as a liver biopsy, which makes it impractical to access the dynamics of cccDNA in patients. Although HBV RNA and HBV core-related antigens (HBcrAg) have been proposed as surrogate markers for evaluating cccDNA activity, they do not necessarily estimate the amount of cccDNA.

Statins enhance extracellular release of hepatitis C virus particles through ERK5 activation.

Statins, such as lovastatin, have been known to inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Statins were reported to moderately suppress hepatitis C virus (HCV) replication in cultured cells harboring HCV RNA replicons. We report here using an HCV cell culture (HCVcc) system that high concentrations of lovastatin (5-20 μg/mL) markedly enhanced the release of HCV infectious particles (virion) in the culture supernatants by up to 40 times, without enhancing HCV RNA replication, HCV protein synthesis, or HCV virion assembly in the cells.

Overcoming antibody-resistant SARS-CoV-2 variants with bispecific antibodies constructed using non-neutralizing antibodies.

A current challenge is the emergence of SARS-CoV-2 variants, such as BQ.1.1 and XBB.

Enterovirus A71 does not meet the uncoating receptor SCARB2 at the cell surface.

Enterovirus A71 (EV-A71) infection involves a variety of receptors. Among them, two transmembrane protein receptors have been investigated in detail and shown to be critical for infection: P-selectin glycoprotein ligand-1 (PSGL-1) in lymphocytes (Jurkat cells), and scavenger receptor class B member 2 (SCARB2) in rhabdomyosarcoma (RD) cells. PSGL-1 and SCARB2 have been reported to be expressed on the surface of Jurkat and RD cells, respectively.

Structural basis of hepatitis B virus receptor binding.

Hepatitis B virus (HBV), a leading cause of developing hepatocellular carcinoma affecting more than 290 million people worldwide, is an enveloped DNA virus specifically infecting hepatocytes. Myristoylated preS1 domain of the HBV large surface protein binds to the host receptor sodium-taurocholate cotransporting polypeptide (NTCP), a hepatocellular bile acid transporter, to initiate viral entry. Here, we report the cryogenic-electron microscopy structure of the myristoylated preS1 (residues 2-48) peptide bound to human NTCP.

Hepatocellular organellar abnormalities following elimination of hepatitis C virus.

Background And Aims: The future development of hepatocellular carcinoma (HCC) in patients after sustained virologic response (SVR) is an important issue. The purposes of this study were to investigate pathological alterations in organelle of the liver of SVR patients and to characterize organelle abnormalities that may be related to carcinogenesis after SVR.

Methods: The ultrastructure of liver biopsy specimens from patients with chronic hepatitis C (CHC) and SVR were compared to cell and mouse models and assessed semi-quantitatively using transmission electron microscopy.

Hepatitis C Virus Disrupts Annexin 5-Mediated Occludin Integrity through Downregulation of Protein Kinase Cα (PKCα) and PKCη Expression, Thereby Promoting Viral Propagation.

Annexins (ANXs) comprise a family of calcium- and phospholipid-binding proteins and are implicated in the hepatitis C virus (HCV) life cycle. Here, we demonstrate a novel role of ANX5 in the HCV life cycle. Comparative analysis by quantitative PCR in human hepatoma cells revealed that ANX2, ANX4, and ANX5 were highly expressed among the ANX family proteins.

A Multicenter Randomized Controlled Trial To Evaluate the Efficacy and Safety of Nelfinavir in Patients with Mild COVID-19.

Nelfinavir, an orally administered inhibitor of human immunodeficiency virus protease, inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) . We conducted a randomized controlled trial to evaluate the clinical efficacy and safety of nelfinavir in patients with SARS-CoV-2 infection. We included unvaccinated asymptomatic or mildly symptomatic adult patients who tested positive for SARS-CoV-2 infection within 3 days before enrollment.

N6-methyladenosine Modification of Hepatitis B Virus RNA in the Coding Region of .

N6-methyladenosine (mA) is a post-transcriptional modification of RNA involved in transcript transport, degradation, translation, and splicing. We found that HBV RNA is modified by mA predominantly in the coding region of . The mutagenesis of methylation sites reduced the HBV mRNA and HBs protein levels.