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.

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.

Analysis of cross-reactivity among flaviviruses using sera of patients with dengue showed the importance of neutralization tests with paired serum samples for the correct interpretations of serological test results for dengue.

Dengue is a febrile illness caused by the dengue virus (DENV) that belongs to the genus Flavivirus in the family Flaviviridae. Cross-reactivity between flaviviruses poses a challenge while interpreting serological test results. In the present study, the cross-reactivity of sera of the patients with dengue, who traveled from Japan to DENV-endemic countries, was analyzed by using an enzyme-linked immunosorbent assay (ELISA) and neutralization test (NT).

Susceptibility of Type I Interferon Receptor Knock-Out Mice to Heartland Bandavirus (HRTV) Infection and Efficacy of Favipiravir and Ribavirin in the Treatment of the Mice Infected with HRTV.

Heartland bandavirus (HRTV) is an emerging tick-borne virus that is distributed in the United States and that causes febrile illness with thrombocytopenia and leukocytopenia. It is genetically close to Dabie bandavirus, which is well known as severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV). The mortality rate of human HRTV infection is approximately 10%; however, neither approved anti-HRTV agents nor vaccines exist.

Immunogenicity and Protective Ability of Genotype I-Based Recombinant Japanese Encephalitis Virus (JEV) with Attenuation Mutations in E Protein against Genotype V JEV.

Genotype V (GV) Japanese encephalitis virus (JEV) has emerged in Korea and China since 2009. Recent findings suggest that current Japanese encephalitis (JE) vaccines may reduce the ability to induce neutralizing antibodies against GV JEV compared to other genotypes. This study sought to produce a novel live attenuated JE vaccine with a high efficacy against GV JEV.

Facilitating the deployment of Japanese human resources for responding global outbreaks of emerging and Re-emerging infectious diseases: A cross-sectional study.

Introduction: In response to global outbreaks of infectious diseases, the need for support from organizations such as the World Health Organization Global Outbreak Alert and Response Network (GOARN) is increasing. Identifying the obstacles and support needs for applicants could increase GOARN deployments from Japan.

Methods: This cross-sectional study involved a web-based, self-administered questionnaire survey targeting Japanese participants in the GOARN Tier 1.

Leu-to-Phe substitution at prM decreases the growth ability of Zika virus and partially reduces its pathogenicity in mice.

Zika virus (ZIKV) is a mosquito-borne flavivirus that causes febrile illness. The recent spread of ZIKV from Asia to the Americas via the Pacific region has revealed unprecedented features of ZIKV, including transplacental congenital infection causing microcephaly. Amino acid changes have been hypothesized to underlie the spread and novel features of American ZIKV strains; however, the relationship between genetic changes and the epidemic remains controversial.

Neuroinvasiveness of the MR766 strain of Zika virus in IFNAR-/- mice maps to prM residues conserved amongst African genotype viruses.

Zika virus (ZIKV) strains are classified into the African and Asian genotypes. The higher virulence of the African MR766 strain, which has been used extensively in ZIKV research, in adult IFNα/β receptor knockout (IFNAR-/-) mice is widely viewed as an artifact associated with mouse adaptation due to at least 146 passages in wild-type suckling mouse brains. To gain insights into the molecular determinants of MR766's virulence, a series of genes from MR766 were swapped with those from the Asian genotype PRVABC59 isolate, which is less virulent in IFNAR-/- mice.

A Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19.

Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Analysis of the Function of the Lymphocytic Choriomeningitis Virus S Segment Untranslated Region on Growth Capacity In Vitro and on Virulence In Vivo.

Lymphocytic choriomeningitis virus (LCMV) is a prototypic arenavirus. The function of untranslated regions (UTRs) of the LCMV genome has not been well studied except for the extreme 19 nucleotide residues of both the 5' and 3' termini. There are internal UTRs composed of 58 and 41 nucleotide residues in the 5' and 3' UTRs, respectively, in the LCMV S segment.

Dengue Virus Serotype 1 Exported to Japan from Côte d'Ivoire, 2019.

Dengue fever outbreaks have been repeatedly reported in Côte d'Ivoire. During the 2019 outbreak, DENV-1 was the predominant strain and phylogenetic analysis of the DENV-1 genome obtained from the present patient who returned to Japan in January 2019 revealed a high homology with the 2013-2014 Southeast Asian strains. In a previous outbreak in 2017, DENV-1 accounted for 5% of the DENV serotypes.

Amino Acid at Position 166 of NS2A in Japanese Encephalitis Virus (JEV) is Associated with In Vitro Growth Characteristics of JEV.

We previously showed that the growth ability of the Japanese encephalitis virus (JEV) genotype V (GV) strain Muar is clearly lower than that of the genotype I (GI) JEV strain Mie/41/2002 in murine neuroblastoma cells. Here, we sought to identify the region in GV JEV that is involved in its low growth potential in cultured cells. An intertypic virus containing the NS1-3 region of Muar in the Mie/41/2002 backbone (NS1-3) exhibited a markedly diminished growth ability in murine neuroblastoma cells.

E and prM proteins of genotype V Japanese encephalitis virus are required for its increased virulence in mice.

We previously showed that the Japanese encephalitis virus (JEV) genotype V (GV) strain Muar exhibits significantly higher virulence in mice than the genotype I (GI) JEV strain Mie/41/2002. In this study, we attempted to identify the region responsible for the increased virulence of GV JEV using recombinant intertypic and single mutant JEVs. Intertypic viruses containing the GV E region in the Mie/41/2002 backbone showed increased pathogenicity in mice.

Increased growth ability and pathogenicity of American- and Pacific-subtype Zika virus (ZIKV) strains compared with a Southeast Asian-subtype ZIKV strain.

We investigated the growth properties and virulence in mice of three Zika virus (ZIKV) strains of Asian/American lineage, PRVABC59, ZIKV/Hu/Chiba/S36/2016 (ChibaS36), and ZIKV/Hu/NIID123/2016 (NIID123), belonging to the three distinct subtypes of this lineage. The American-subtype strain, PRVABC59, showed the highest growth potential in vitro, whereas the Southeast Asian-subtype strain, NIID123, showed the lowest proliferative capacity. Moreover, PRVABC59- and NIID123-infected mice showed the highest and lowest viremia levels and infectious virus levels in the testis, respectively, and the rate of damaged testis in PRVABC59-infected mice was higher than in mice infected with the other two strains.

Analysis of cross-reactivity between flaviviruses with sera of patients with Japanese encephalitis showed the importance of neutralization tests for the diagnosis of Japanese encephalitis.

Japanese encephalitis (JE) is one of the most important viral encephalitis in Asia. JE is caused by the Japanese encephalitis virus (JEV), which belongs to the genus Flavivirus, family Flaviviridae. The diagnosis of JE is usually based on serological assays, and it has been reported that cross-reactivity between flaviviruses has complicated the interpretations of results from serological assays.

Dengue Virus Type 2 Infection in a Traveler Returning from Saudi Arabia to Japan.

In July 2018, a Japanese traveler returning from Saudi Arabia was diagnosed with dengue. The dengue virus type 2 gene was detected from a whole blood sample. Phylogenetic analysis revealed that the strain was clustered with isolates from Singapore and India.

Neutralization Potency of Sera from Vietnamese Patients with Japanese Encephalitis (JE) against Genotypes I and V JE Viruses.

Japanese encephalitis virus (JEV) is classified into 5 genotypes (GI, GII, GIII, GIV, and GV), and the GI and GIII strains are the most widely distributed in JE endemic areas. In recent years, GV JEV has been detected in China and Korea, suggesting that GV JEV may invade other JE endemic areas, including Vietnam, and that more attention should be paid to the JEV strains circulating in these areas. In this study, we investigated the neutralization ability of the sera collected from 22 Vietnamese patients with JE who lived in northern Vietnam against the GI and GV JEV strains.

Comparison of Neutralizing Antibody Titers against Japanese Encephalitis Virus Genotype V Strain with Those against Genotype I and III Strains in the Sera of Japanese Encephalitis Patients in Japan in 2016.

Japanese encephalitis (JE) is an acute viral disease caused by the Japanese encephalitis virus (JEV). JEV strains are classified into 5 genotypes (I-V). JEV genotype V strains have never been detected in Japan to date, but they were recently detected in South Korea.

A Japanese Encephalitis Patient Presenting with Parkinsonism with Corresponding Laterality of Magnetic Resonance and Dopamine Transporter Imaging Findings.

Japanese encephalitis (JE) survivors often present with nigrostriatal aftereffects with parkinsonian features. A 67-year-old woman with JE showed right-dominant clinical parkinsonism and left-dominant substantia nigra lesions after magnetic resonance imaging (MRI). Dopamine transporter (DAT) imaging using I-labeled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (I-FP-CIT) revealed a corresponding left-dominant decrease.

Characterization of large and small-plaque variants in the Zika virus clinical isolate ZIKV/Hu/S36/Chiba/2016.

An Asian/American lineage Zika virus (ZIKV) strain ZIKV/Hu/S36/Chiba/2016 formed 2 types in plaque size, large and small. Genomic analysis of the plaque-forming clones obtained from the isolate indicated that the clones forming small plaques commonly had an adenine nucleotide at position 796 (230 in the amino acid sequence), while clones forming large plaques had a guanine nucleotide (230) at the same position, suggesting that this position was associated with the difference in plaque size. Growth kinetics of a large-plaque clone was faster than that of a small-plaque clone in Vero cells.

A Case of Dengue Fever Imported from Burkina Faso to Japan in October 2016.

Dengue fever remains underreported in Africa due to a lack of awareness among healthcare providers, the presence of other febrile illnesses, and insufficient laboratory testing. We present a case of dengue fever imported from Burkina Faso to Japan, where an outbreak of dengue was reported on October 18, 2016. Phylogenetic analysis revealed that the isolate from our patient belonged to a distinct cluster of sylvatic dengue viruses, suggesting that dengue viruses have been maintained in mosquitoes and human cycles in Burkina Faso for more than 30 years.

Dengue Virus Type 2 in Travelers Returning to Japan from Sri Lanka, 2017.

In June 2017, dengue virus type 2 infection was diagnosed in 2 travelers returned to Japan from Sri Lanka, where the country's largest dengue fever outbreak is ongoing. Travelers, especially those previously affected by dengue fever, should take measures to avoid mosquito bites.

Dengue Virus Exported from Côte d'Ivoire to Japan, June 2017.

Since April 2017, a dengue fever outbreak has been ongoing in Côte d'Ivoire. We diagnosed dengue fever (type 2 virus) in a traveler returning to Japan from Côte d'Ivoire. Phylogenetic analysis revealed strain homology with the Burkina Faso 2016 strain.