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To improve current infertility treatments, it is important to understand the pathophysiology of implantation failure. However, many molecules are involved in the normal biological process of implantation and the roles of each molecule and the molecular mechanism are not fully understood. This review highlights the hemagglutinating virus of Japan (HVJ; Sendai virus) envelope (HVJ-E) vector, which uses inactivated viral particles as a local and transient gene transfer system to the murine uterus during the implantation period in order to investigate the molecular mechanism of implantation. In vivo screening in mice using the HVJ-E vector system suggests that signal transducer and activator of transcription-3 (Stat-3) could be a diagnostic and therapeutic target for women with a history of implantation failure. The HVJ-E vector system hardly induces complete defects in genes; however, it not only suppresses but also transiently overexpresses some genes in the murine uterus. These features may be useful in investigating the pathophysiology of implantation failure in women. [ABSTRACT FROM AUTHOR]

To assess the effects of seasonal irrigation subsidies from paddy fields, spatiotemporal changes in diets of detritus feeders including nereidid polychaetes Hediste diadroma and H. atoka (facultative suspension feeders) and Tylorrhynchus osawai (surface-deposit feeder) were examined in Idoura Lagoon, Sendai Bay, Japan, using carbon and nitrogen stable isotope ratios (d13C and d15N). d13C ratios of Hediste species were much lower near a freshwater input (St. IB; -25.6 to -18.2‰) than in a seaward area (St. IA; -17.9 to -14.3‰), highlighting the assimilation of river subsidies in river-affected habitats. A d13C-based isotopic mixing model showed that riverine phytoplankton and detrital matters became the major diet of Hediste species in August and December at St. IB (60 to 72%), which corresponded to the supply of irrigation drainage to the area. Contrastingly the contribution of microphytobenthos increased sharply in March at both stations (55 to 83%) because of benthic diatom blooms. These emphasize that the Hediste species can change their feeding modes (i.e., suspension- and deposit-feeding) depending on food availability in the habitat. In winter and/or spring, d13C of H. diadroma negatively correlated with their body size, suggesting size-dependent variation in food utilization. d13C ratios of the sympatric deposit-feeders and suspension-feeding bivalves were seasonally more stable, depending mainly on microphytobenthos and river derived materials, respectively. These suggest that a certain group of estuarine consumers including Hediste species act as significant links between terrestrial and estuarine food webs by incorporating riverine terrestrial subsidies to benthic secondary production in estuaries. [ABSTRACT FROM AUTHOR]

Despite recent advance in immunotherapy agents, safe new therapies that enhance the effects of immune checkpoint inhibitors are still required to develop. We previously demonstrated that hemagglutinating virus of Japan-envelope (HVJ-E) induced not only direct tumor cell death but also antitumor immunity through the activation of T and natural killer (NK) cells, thereafter, developed a manufacturing process of HVJ-E (GEN0101) for clinical use. We here performed a phase Ia clinical trial of intratumoral GEN0101 administration in six patients with stage IIIC or IV malignant melanoma. The primary aim was to evaluate the safety and tolerability of GEN0101, and the secondary aim was to examine the objective tumor response. Patients were separated into two groups (n = 3 each) and received a low dose of 30,000 and high dose of 60,000 mNAU of GEN0101. All patients completed a two-week follow-up evaluation without severe adverse events. The overall response rate was 33% (2 of 6), with 2 partial responses in the high-dose group and 2 with stable disease, and 2 with progressive disease in the low-dose group. Local complete or partial responses were observed in 11 of 18 (61%) target lesions. One patient demonstrated shrinkage of lung metastases after the treatment. The activity of NK cells and interferon-γ levels were increased in the circulation, indicating augmentation of antitumor immunity by GEN0101. This trial showed not only the safety and tolerability but also the significant antitumor effect of GEN0101, suggesting that GEN0101 might be a promising new drug for patients with advanced melanoma. [ABSTRACT FROM AUTHOR]

Ischemic neuropathy is common in subjects with critical limb ischemia, frequently causing chronic neuropathic pain. However, neuropathic pain caused by ischemia is hard to control despite the restoration of an adequate blood flow. Here, we used a rat model of ischemic-reperfusion nerve injury (IRI) to investigate possible effects of hepatocyte growth factor (HGF) against ischemic neuropathy. Hemagglutinating virus of Japan (HVJ) liposomes containing plasmids encoded with HGF was delivered into the peripheral nervous system by retrograde axonal transport following its repeated injections into the tibialis anterior muscle in the right hindlimb. First HGF gene transfer was done immediately after IRI, and repeated at 1, 2 and 3 weeks later. Rats with IRI exhibited pronounced mechanical allodynia and thermal hyperalgesia, decreased blood flow and skin temperature, and lowered thresholds of plantar stimuli in the hind paw. These were all significantly improved by HGF gene transfer, as also were sciatic nerve conduction velocity and muscle action potential amplitudes. Histologically, HGF gene transfer resulted in a significant increase of endoneurial microvessels in sciatic and tibial nerves and promoted nerve regeneration which were confirmed by morphometric analysis. Neovascularization was observed in the contralateral side of peripheral nerves as well. In addition, IRI elevated mRNA levels of P2X3 and P2Y1 receptors, and transient receptor potential vanilloid receptor subtype 1 (TRPV1) in sciatic nerves, dorsal root ganglia and spinal cord, and these elevated levels were inhibited by HGF gene transfer. In conclusion, HGF gene transfer is a potent candidate for treatment of acute ischemic neuropathy caused by reperfusion injury, because of robust angiogenesis and enhanced nerve regeneration. [ABSTRACT FROM AUTHOR]

A novel genus within the Orthomyxoviridae family was identified in the USA and named Influenza D virus (IDV). Bovine have been proposed to be the primary host and three main viral lineages (D/OK-like, D/660-like and D/Japan-like) have been described. Experimental infections were so far performed in swine, ferret, calf and guinea pig, in order to study IDV pathogenesis. We developed a murine experimental model to ease the study of IDV pathogenesis and immune response. DBA/2 mice were inoculated with 105 TCID50 of D/bovine/France/5920/2014 (D/OK-like). No clinical signs and weight loss were observed. Viral replication was observed mainly in the upper respiratory tract (nasal turbinates) but also in lower respiratory tract of infected mice, with a peak at 4 days post-infection. Moreover, the virus was also detected in the intestines. All infected mice seroconverted by 14 days post infection. Transcriptomic analyses demonstrated that IDV induced an activation of pro inflammatory genes such as IFN-γ and CCL2. Inoculation of NFκB-luciferase and Ifnar1-/- mice demonstrated that IDV induced mild inflammation and that type I interferons response was not necessary in IDV clearance. Adaptation of IDV by serial passages in mice was not sufficient to induce disease or increased pathogenesis. Taken together, present data and comparisons with the calf model show that our mouse model allows for the study of IDV replication and fitness (before selected viruses may be inoculated on calves) and also of the immune response. [ABSTRACT FROM AUTHOR]

Influenza D virus (IDV) can potentially cause respiratory diseases in livestock. We isolated a new IDV strain from diseased cattle in Japan; this strain is phylogenetically and antigenically distinguished from the previously described IDVs. [ABSTRACT FROM AUTHOR]

Summary: The influenza D virus, a new member of the Orthomyxoviridae family, is predominantly found in cattle. Although viral pathology and clinical disease in cattle appear mild, this virus plays an important role as a trigger of bovine respiratory disease (BRD). BRD is a costly illness worldwide. Thus, epidemiological surveys of the influenza D virus are necessary. Here, we conducted a molecular epidemiological survey for the influenza D virus in healthy and respiratory‐diseased cattle in Japan. We found that 2.1% (8/377) of the cattle were infected with influenza D. The cattle with and without respiratory symptoms had approximately equal amounts of the virus. A full‐genome sequence analysis revealed that the influenza D virus that was isolated in Japan formed an individual cluster that was distinct from the strains found in other countries. These results suggest that this virus might have evolved uniquely in Japan over a long period of time and that the viral pathology of Japanese strains might be different from the strains found in other countries. Continuous surveillance is required to determine the importance of this virus and to characterize its evolution. [ABSTRACT FROM AUTHOR]

Cattle are major reservoirs of the provisionally named influenza D virus, which is potentially involved in the bovine respiratory disease complex. Here, we conducted a serological survey for the influenza D virus in Japan, using archived bovine serum samples collected during 2010–2016 from several herds of apparently healthy cattle in various regions of the country. We found sero-positive cattle across all years and in all the prefectural regions tested, with a total positivity rate of 30.5%, although the positivity rates varied among regions (13.5–50.0%). There was no significant difference in positivity rates for Holstein and Japanese Black cattle. Positivity rates tended to increase with cattle age. The herds were clearly divided into two groups: those with a high positive rate and those with a low (or no) positive rate, indicating that horizontal transmission of the virus occurs readily within a herd. These data demonstrate that bovine influenza D viruses have been in circulation for at least 5 years countrywide, emphasizing its ubiquitous distribution in the cattle population of Japan. [ABSTRACT FROM AUTHOR]

ABSTRACT To clarify the epidemiology of viral acute respiratory infections (ARIs), 305 human parainfluenza virus types 1 (HPIV1), 154 HPIV2 and 574 HPIV3 strains were isolated from 16,962 nasopharyngeal swabs obtained between 2002 and 2011 at pediatric clinics in Yamagata, Japan. The total isolation frequency for HPIV1-3 was 6.1%. Unlike HPIV1 infections, HPIV3 showed clear seasonality with yearly outbreaks in the spring-summer season. HPIV2 tended to appear biannually in autumn-winter. Although no reliable techniques for the laboratory diagnosis of these infections have been established, the present results suggest that HPIV1-3 are an important causative agent of ARIs in children. [ABSTRACT FROM AUTHOR]

Objective. Mycobacterium tuberculosis infection is a major global threat to human health. The only tuberculosis (TB) vaccine currently available is bacillus Calmette-Guérin (BCG), although it has no efficacy in adults. Therefore, the development of a novel vaccine against TB for adults is desired. Method. A novel TB vaccine expressing mycobacterial heat shock protein 65 (HSP65) and interleukin-12 (IL-12) delivered by the hemagglutinating virus of Japan- (HVJ)- envelope was evaluated against TB infection in mice. Bacterial load reductions and histopathological assessments were used to determine efficacy. Results. Vaccination by BCG prime with IgHSP65+murine IL-12/HVJ-envelope boost resulted in significant protective efficacy (>10, 000-fold versus BCG alone) against TB infection in the lungs of mice. In addition to bacterial loads, significant protective efficacy was demonstrated by histopathological analysis of the lungs. Furthermore, the vaccine increased the number of T cells secreting IFN-?. Conclusion. This vaccine showed extremely significant protection against TB in a mouse model, consistent with results from a similar paper on cynomolgus monkeys. The results suggest that further development of the vaccine for eventual testing in clinical trials may be warranted. [ABSTRACT FROM AUTHOR]

The article focuses on the research presented by Katsumi Mizuta and colleagues on the genetic analysis of hemagglutinin-neuraminidase glycoprotein gene in human parainfluenza virus type 1 (HPIV1) isolates derived from the patient with acute respiratory infection in Yamagata, Japan. It mentions that (HPIV1) causes acute respiratory infections (ARI). It states that hemagglutinin-neuraminidase (HN) glycoprotein related HPIV1 is a major antigen for ARI.

The article reports on a study that examines approaches in generation of human induced pluripotent stem cells (hiPSCs) from human terminally differentiated circulating T cells (hTDCTCs) in Japan. Researchers demonstrate that a combination of activated T cell cultivation and a temperature-sensitive mutated Sendai virus allows efficient and safe generation of hiPSCs. Findings of the study showed the development of a minimally invasive method for hiPSC generation without genomic integration.

AbstractIn a previous study, it was found that the synthesis of hemagglutinating virus of Japan (HVJ; Sendai virus)-specific proteins was inhibited at the transcriptional level at 41° in LLC-MK2 cells. During an investigation of the temperature sensitivity of HVJ production in other host cells, the synthesis of HVJ-specific proteins was recognized even at 41° in Vero cells. Viral production, however, was not detected, indicating the inhibition of steps after the synthesis of viral proteins. Hemadsorption activity was not detected at 41°, suggesting problems with the envelope proteins, especially hemagglutinin-neuraminidase (HN) protein, at the cell membrane. Immunofluorescent staining and surface immunoprecipitation showed that HN protein was not present on the surface in spite of its localization in the cytoplasm. Further, analysis of the cell membrane fraction suggested that fusion (F) protein was integrated into the cell membrane but HN protein was not at 41°. Electron microscopic observation showed that budding sites with spike structures formed and nucleocapsids assembled under the sites at 41° without HN protein, although budded HVJ virions were not detected. At this time, F protein was exposed to the cell membrane and interacted with matrix and nucleocapsid proteins. The results suggested that the suppression of HVJ production at 41° was due to the absence of HN protein in the membrane of Vero cells.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Vesicular stomatitis virus (VSV), the founding member of the mononegavirus order (Mononegavirales), was found to be a negative strand RNA virus in the 1960s, and since then the number of such viruses has continually increased with no end in sight. Sendai virus (SeV) was noted soon afterwards due to an outbreak of newborn pneumonitis in Japan whose putative agent was passed in mice, and nowadays this mouse virus is mainly the bane of animal houses and immunologists. However, SeV was important in the study of this class of viruses because, like flu, it grows to high titers in embryonated chicken eggs, facilitating the biochemical characterization of its infection and that of its nucleocapsid, which is very close to that of measles virus (MeV). This review and opinion piece follow SeV as more is known about how various mononegaviruses express their genetic information and carry out their RNA synthesis, and proposes a unified model based on what all MNV have in common. [ABSTRACT FROM AUTHOR]

Influenza D virus (IDV), which is a new member of the Orthomyxoviridae family, is potentially involved in bovine respiratory diseases (BRDs). Bovine IDVs (BIDVs) from Japan have been distributed nationwide since 2010 and are genetically distinct from foreign IDVs. We isolated BIDVs from three BRD outbreaks, in Hokkaido during 2018–2020, to understand their genetic and antigenic characteristics. Retrospective surveillance was performed using sera collected throughout the last decade in Hokkaido to investigate BIDV existence. Three BIDVs were isolated using cell culture. Comparative and phylogenetic analyses using sequence data of the three BIDVs and IDVs from Japan and other countries available in GenBank demonstrated that Japanese BIDVs, including the three BIDV isolates, were genetically distinct from other IDVs. Genotype classifications based on the rotavirus genotype classification revealed multiple genotypes of RNA segments 1–7. Two BIDVs were of a new genotype, different from those of other Japanese BIDVs. Neutralization assays against two BIDVs with different genotypes using sera collected in acute and recovery phases of BRD revealed differences in cross-reactivity to heterogenous BIDVs. Retrospective surveillance suggested that BIDV existed in Hokkaido, in 2009. Our findings suggest that BIDVs of different genotypes and antigenicity are distributed and maintained in Hokkaido and provide new insights into molecular characteristics and the evolution of IDVs. [ABSTRACT FROM AUTHOR]