Nipah Virus Antibodies in Bats, the Philippines, 2013-2022.

In 2014, an outbreak of zoonotic Nipah virus (NiV) occurred on Mindanao Island, the Philippines. We investigated the prevalence of NiV in Philippine bats. Because neutralizing antibodies were detected in insectivorous bats on Siargao Island, public health officials should consider that the distribution range of NiV is not limited to Mindanao Island.

Bivalent single-domain antibodies show potent mpox virus neutralization through M1R antigen.

Despite the recent mpox outbreak raising global concerns, no fully validated antiviral treatment exists, highlighting the urgent need for effective therapeutics. Here, by taking advantage of the preparation technology for single-domain (VHH) antibodies, we generated VHHs targeting the six major mpox virus (MPXV) surface antigens. Although neutralization activity of these monoclonal VHH monomers was negligible, bivalent VHHs against MPXV-M1R (bi-M1A8 and bi-M1C2) improved the antigen binding affinity by up to over 400-fold compared with the monomer VHH and thus produced neutralizing activity against MPXV.

Riboflavin transporter: evidence of a role as entry receptor for chimpanzee endogenous retrovirus.

Endogenous retroviruses (ERVs) are remnants of ancestral viral infections in germ cells that constitute a substantial proportion of the mammalian genome and are assumed to provide molecular fossil records of ancient infections. Analysis of these sequences may reveal the mechanisms of virus-host co-evolution, viral endogenization, and extinction. Chimpanzee endogenous retrovirus 1 (CERV1), a gamma retrovirus, is estimated to have circulated within primates for ~10 million years, although it is now apparently extinct.

and characterization of a bat merbecovirus with ACE2- and DPP4-independent cell entry.

Unlabelled: Betacoronaviruses, which have caused three human outbreaks within the last two decades, are thought to originate from bats, raising the concern that bat coronaviruses could cause a novel human outbreak in the future. To determine whether the bat merbecovirus EjCoV-3 strain, previously detected in in Japan, has the potential to infect humans, we analyzed its cellular entry mechanism. Cellular entry of EjCoV-3 via the spike protein requires protease treatment and is mediated by an unknown receptor, other than DPP4 or ACE2.

Development and clinical evaluation of a MPXV antigen-detecting rapid diagnostic test.

To address the global emergence of mpox after the 2022 epidemic, a rapid and accurate diagnostic tool is needed at the point of care to identify individuals infected with mpox virus (MPXV) to prevent and control the spread of the virus. We designed an antigen-detecting rapid diagnostic test that exclusively detects MPXV without cross-reacting with the vaccinia virus by developing monoclonal antibodies against the MPXV nuclear capsid protein A5L (MPXV-A5L). The test results indicated that the detection limits were established at 0.

Cytokine storm and vascular leakage in severe dengue: insights from single-cell RNA profiling.

Severe dengue is characterized by vascular leakage triggered by a hyperinflammatory response, though the underlying mechanisms remain unclear. Our previous mouse model study highlighted the importance of small intestine in severe disease and identified key cytokines (IL-17A, TNF-α, and IL-6) involved. Here, we used a Fixed RNA Profiling assay to characterize key cytokine- and effector-producing cells, along with their receptor expression.

N-glycosylation of viral glycoprotein is a novel determinant for the tropism and virulence of highly pathogenic tick-borne bunyaviruses.

Severe fever with thrombocytopenia syndrome (SFTS) virus, a tick-borne bunyavirus, causes a severe/fatal disease termed SFTS; however, the viral virulence is not fully understood. The viral non-structural protein, NSs, is the sole known virulence factor. NSs disturbs host innate immune responses and an NSs-mutant SFTS virus causes no disease in an SFTS animal model.

Mice, myeloid cells, and dengue: a new model for unraveling vascular leakage mysteries.

Introduction: Severe dengue is thought to be caused by an excessive host immune response.

Methods: To study the pathogenesis of severe dengue, we developed a novel model using LysM Cre mice carrying depleted expression only in subsets of murine myeloid cells.

Results: Although dengue virus (DENV) clinical isolates were not virulent in LysM Cre mice, mouse-adapted DV1-5P7Sp and DV3P12/08P4Bm, which were obtained by passaging the spleen or bone marrow of mice, demonstrated 100% lethality with severe vascular leakage in the liver and small intestine.

Lethal severe fever with thrombocytopenia syndrome virus infection causes systemic germinal centre failure and massive T cell apoptosis in cats.

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is a fatal viral disease characterized by high fever, thrombocytopenia, leukopenia, and multi-organ haemorrhage. Disruption of the humoral immune response and decreased lymphocyte numbers are thought to contribute to the disease severity. These findings have been obtained through the analysis of peripheral blood leukocytes in human patients, whereas analysis of lymph nodes has been limited.

[Study of practical biorisk management in microbiological containment laboratories].

Biosafety Level 4 facilities have been established in our country to promote research and development and national capacity of diagnostic test systems for infectious diseases, including highly pathogenic viruses. In particular, the operation of a suit-type laboratory requiring positive pressure protective suits is a first for our country, and it is necessary to establish unique safety management technology. With the support of the Research Program on Emerging and Re-emerging Infectious Diseases of the Japan Agency for Medical Research and Development (AMED), we conducted research entitled "Study of Practical Biorisk Management in the Microbiological Containment Laboratories" from 2021 to 2023, with the aim of improving biosafety management technology in Japan.

Pathological and virological findings of type I interferon receptor knockout mice upon experimental infection with Heartland virus.

Heartland virus (HRTV) causes generalized symptoms, severe shock, and multiple organ failure. We previously reported that interferon-α/β receptor knockout (IFNAR) mice infected intraperitoneally with 1 × 10 tissue culture-infective dose (TCID) of HRTV died, while those subcutaneously infected with the same dose of HRTV did not. The pathophysiology of IFNAR mice infected with HRTV and the mechanism underlying the difference in disease severity, which depends on HRTV infection route, were analyzed in this study.

Seroprevalence for severe fever with thrombocytopenia syndrome virus among the residents of Miyazaki, Japan: An epidemiological study.

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease caused by the SFTS virus (SFTSV). The Miyazaki Prefecture has the highest number of SFTS cases in Japan and requires countermeasures for prevention. In this study, we aimed to conduct an epidemiological survey in Miyazaki Prefecture to determine the exposure conditions of SFTSV by measuring the seroprevalence among residents of Miyazaki and to evaluate the factors that influence the endemicity of SFTS.

Dengue virus infection induces selective expansion of Vγ4 and Vγ6TCR γδ T cells in the small intestine and a cytokine storm driving vascular leakage in mice.

Dengue is a major health problem in tropical and subtropical regions. Some patients develop a severe form of dengue, called dengue hemorrhagic fever, which can be fatal. Severe dengue is associated with a transient increase in vascular permeability.

Identification of IMP Dehydrogenase as a Potential Target for Anti-Mpox Virus Agents.

Mpox virus (formerly monkeypox virus [MPXV]) is a neglected zoonotic pathogen that caused a worldwide outbreak in May 2022. Given the lack of an established therapy, the development of an anti-MPXV strategy is of vital importance. To identify drug targets for the development of anti-MPXV agents, we screened a chemical library using an MPXV infection cell assay and found that gemcitabine, trifluridine, and mycophenolic acid (MPA) inhibited MPXV propagation.

Evaluating the Immunogenicity and Safety of a Smallpox Vaccine to Monkeypox in Healthy Japanese Adults: A Single-Arm Study.

Monkeypox (mpox) is an acute exanthematous disease caused by the monkeypox virus (MPXV). Since May 2022, patients with mpox have been reported worldwide, mainly in Europe and the Americas. In Japan, LC16"KMB," which is a smallpox vaccine derived from a dried cell culture, against mpox, has been approved.

Rapid whole genome sequencing methods for RNA viruses.

RNA viruses are the etiological agents of many infectious diseases. Since RNA viruses are error-prone during genome replication, rapid, accurate and economical whole RNA viral genome sequence determination is highly demanded. Next-generation sequencing (NGS) techniques perform whole viral genome sequencing due to their high-throughput sequencing capacity.

The combination of levodopa with levodopa-metabolizing enzyme inhibitors prevents severe fever with thrombocytopenia syndrome virus infection in vitro more effectively than single levodopa.

Severe fever with thrombocytopenia syndrome is a hemorrhagic fever caused by a tick-borne infection. The causative agent, Dabie bandavirus, is also called the severe fever with thrombocytopenia syndrome virus (SFTSV). Ogawa et al.

Inhibition of cellular RNA methyltransferase abrogates influenza virus capping and replication.

Orthomyxo- and bunyaviruses steal the 5' cap portion of host RNAs to prime their own transcription in a process called "cap snatching." We report that RNA modification of the cap portion by host 2'-O-ribose methyltransferase 1 (MTr1) is essential for the initiation of influenza A and B virus replication, but not for other cap-snatching viruses. We identified with in silico compound screening and functional analysis a derivative of a natural product from , called trifluoromethyl-tubercidin (TFMT), that inhibits MTr1 through interaction at its -adenosyl-l-methionine binding pocket to restrict influenza virus replication.