We previously reported that the Japanese encephalitis virus (JEV) strain Mie/41/2002 has weak pathogenicity compared with the laboratory strain Beijing-1. To identify the determinants of its growth nature and pathogenicity, we produced intertypic viruses, rJEV(EB1-M41), rJEV(nEB1-M41) and rJEV(cEB1-M41), which contained the entire, the N-terminal, and the C-terminal half, respectively, of the Beijing-1 E region in the Mie/41/2002 background. The growth of rJEV(EB1-M41) in mouse neuroblastoma N18 cells and virulence in mice were similar to those of Beijing-1. rJEV(nEB1-M41) propagated in N18 cells to the same extent as did Beijing-1. Furthermore, we produced mutant viruses with single amino acid substitutions in the N-terminal half of the Mie/41/2002 E region. A Ser-123-Arg mutation in the Mie/41/2002 E protein exhibited significantly increased growth rate in N18 cells and virulence in mice. These results indicate that the position 123 in the E protein is responsible for determining the growth properties and pathogenicity of JEV.

Significance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population.

Background: The number of confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Japan are substantially lower in comparison to the US and UK, potentially due to the under-implementation of polymerase chain reaction (PCR) tests. Studies reported that more than half of the SARS-CoV-2 infections are asymptomatic, confirming the importance for conducting seroepidemiological studies. Although the seroepidemiological studies in Japan observed a reported prevalence of 0.10% in Tokyo, 0.17% in Osaka, and 0.03% in Miyagi, sampling bias was not considered. The study objective was to assess the seroprevalence of SARS-CoV-2 in a random sample of households in Utsunomiya City in Tochigi Prefecture, Greater Tokyo, Japan. Methods: We launched the Utsunomiya COVID-19 seROprevalence Neighborhood Association (U-CORONA) Study to assess the seroprevalence of COVID-19 in Utsunomiya City. The survey was conducted between 14 June 2020 and 5 July 2020, in between the first and second wave of the pandemic. Invitations enclosed with a questionnaire were sent to 2,290 people in 1,000 households randomly selected from Utsunomiya basic resident registry. Written informed consent was obtained from all participants. The level of IgG antibodies to SARS-CoV-2 was assessed by chemiluminescence immunoassay analysis. Results: Among 2,290 candidates, 753 returned the questionnaire and 742 received IgG tests (32.4 % participation rate). Of the 742 participants, 86.8% were 18 years or older, 52.6% were women, 71.1% were residing within 10 km from the test clinic, and 89.2% were living with another person. The age and sex distribution, distance to clinic and police district were similar with those of non-participants, while the proportion of single-person households was higher among non-participants than participants (16.2% vs. 10.8%). We confirmed three positive cases through quantitative antibody testing. No positive cases were found among the people who live in the same household as someone with positive. All cases were afebrile. The estimated unweighted and weighted prevalence of SARS-CoV-2 infection were 0.40% (95% confidence interval: 0.08-1.18%) and 1.23% (95% confidence interval: 0.17-2.28%), respectively. Conclusion: This study suggests the importance of detecting all cases using PCR or antigen testing, not only at a hospital, but also in areas where people assemble. Further prospective studies using this cohort are needed to monitor SARS-CoV-2 antibody levels.

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BackgroundDifficult-to-treat infections caused by rapidly growing mycobacteria (RGM) are increasingly observed in clinical settings. However, studies on antimicrobial susceptibilities and effective treatments against RGM in Japan are limited.MethodsWe conducted susceptibility testing of potential antimicrobial agents, including tigecycline and tebipenem, against RGM. Clinical RGM isolates were collected from a university hospital in Japan between December 2010 and August 2013. They were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and the sequencing of 16S rRNA, rpoB, and hsp65 genes. The samples were utilized for susceptibility testing using 16 antimicrobials, with frozen broth microdilution panels.ResultsForty-two isolates were obtained: 13, Mycobacterium abscessus complex; 12, Mycobacterium chelonae; 9, Mycobacterium fortuitum; and 8, M. fortuitum group species other than M. fortuitum. Different antimicrobial susceptibility patterns were observed between RGM species. Clarithromycin-susceptible strain rates were determined to be 0, 62, and 100% for M. fortuitum, M. abscessus complex, and M. chelonae, respectively. M. abscessus complex (100%) and >80% M. chelonae isolates were non-susceptible, while 100% M. fortuitum group isolates were susceptible to moxifloxacin. Linezolid showed good activity against 77% M. abscessus complex, 89% M. fortuitum, and 100% M. chelonae isolates. Regardless of species, all tested isolates were inhibited by tigecycline at very low minimal inhibitory concentrations (MICs) of ≤0.5 μg/mL. MICs of tebipenem, an oral carbapenem, were ≤4 μg/mL against all M. fortuitum group isolates.ConclusionsOur study demonstrates the importance of correct identification and antimicrobial susceptibility testing, including the testing of potential new agents, in the management of RGM infections.

The first 84 nt in the 3' non-translated region (3' NTR) of dengue type 1 virus (DENV-1) exhibit lower levels of conservation than the other regions; this region is named the variable region (VR). The VR is further divided into two subregions: a 5'-terminal hypervariable region (HVR) and a 3'-terminal semi-variable region (SVR). Recent reports suggested that the VR of DENV-2 is required for efficient virus growth in mammalian cells. To investigate whether this is also true for the VR of DENV-1, deletion or replacement mutations were introduced into the VR by using recombinant DENV-1 cDNA clones. Recombinant viruses with deletion of either or both subregions exhibited reduced growth properties compared with the original virus. Mutants with incompletely reversed or unrelated sequences in the HVR demonstrated growth properties similar to those of the original virus. However, a replacement mutation in the SVR did not cause recovery of growth properties. Furthermore, the amount of viral RNA was decreased in Vero cells infected with the growth-attenuated mutant viruses. Results of reporter translation assays suggest that VR mutations may not affect the translation process of DENV-1. These data indicate that the VR is important for DENV-1 replication and is associated with the accumulation of DENV-1 RNA in mammalian cells, and that the HVR and SVR in the VR may have different roles in DENV-1 replication.

Aggressive screening and vaccination of susceptible HCWs was essential regardless of age. Prevaccination serologic screening using a combination of HI assay and EIA was more economical for measles and mumps.

Dengue virus type 1 (DENV-1), which was responsible for the dengue fever outbreak in Yap State, Micronesia, in 2004, was isolated from serum samples of 4 dengue patients in Japan. Genome sequencing demonstrated that this virus belonged to genotype IV and had a 29-nucleotide deletion in the 3´ noncoding region.