Search

The Indo-Pacific region is said to be the center of the 21st century, unlike the Asia-Pacific in the 20th century. In the region, China is emerging rapidly in terms of economic strength, defense capability, and international presence. The US and other concerned countries are striving to cope with the new development. It looks that the US manages to somehow retain its Pax Americana as in the latter half of the last century. China which dreams to head for Pax Sinica has been implementing various measures including removing unfavorable circumstances to promote its dream. At the moment, it is hard to make prompt predictions on how these two Pax would be going. The key question would be ways to deal with China. Typical policies now under implementation are engaging policy represented by the RCEP and balancing policy by the Quad. These two policies have a timeline of short-term policy and middle-term policy. Perhaps, contents of the policies would be finalized depending upon China’s economic development as one of the major factors. To bring about peace and stability of the region, in tandem with them, it might be necessary to bring about a regional order of the Indo-Pacific where it has been lacking. The close relations of Japan and India could be utilized for such a purpose also. Although COVID-19 is afflicting the whole region, it is hoped that the pandemic could be overcome by vaccines and other measures in the near future. It is the right time now to ponder over the future direction of the Indo-Pacific region before it is too late.

Purpose: This review investigated the effectiveness of adjuvant therapy combined with constraint-induced movement therapy (CIMT) in improving the paretic upper limb functionality in adults with stroke sequelae during the subacute to chronic rehabilitation phase., Materials and Methods: In this systematic review and meta-analysis of randomized controlled trials (RCT), electronic databases, including PubMed, Web of Science, CINAHL, and MEDLINE, were searched. We included RCTs that investigated the outcomes of adjuvant therapy (i.e. other therapies) added to CIMT compared with CIMT alone. Key trial findings were qualitatively synthesized and analyzed. This meta-analysis examined variables, such as mean scores and standard deviations, using the following outcome measures: Fugl-Meyer Assessment (FMA) upper limb items, Action Research Arm Test (ARAT), Amount of Use (AOU) of Motor Activity Log (MAL), and Quality of Movement (QOM) of MAL., Results: Eighteen eligible RCTs were included in the analysis. Adding CIMT to adjunctive therapy significantly improved FMA compared with CIMT alone (mean difference [MD] 4.02, 95% confidence interval [CI] 2.60-5.44; I 2 = 85%; 15 studies; 330 participants). Similarly, the ARAT and MAL-AOU scores improved significantly., Conclusions: CIMT combined with several adjunctive therapies effectively improved upper limb function.

Serving size may be the appropriate reference for calculating food nutritional value. We aimed to assess the nutritional values of Japanese foods based on serving sizes rather than per 100 g by adapting the Meiji Nutritional Profiling System (Meiji NPS). Given the variability in serving sizes across countries, we used Japanese serving sizes to calculate the Meiji NPS scores. We confirmed the convergent validity of the Meiji NPS scores per serving size with the Nutrient-Rich Food Index 9.3 using Spearman's correlation coefficients (r = 0.51, p < 0.001). Food groups recommended by official guidelines, such as pulses, nuts and seeds, fish and seafood, fruits, vegetables, and milk and milk products, scored relatively high. Furthermore, the nutrient density scores of food items with small serving sizes, such as mushrooms, algae, seasonings, and fats and oils, were moderated when calculated by per serving size, despite having considerably higher or lower scores per 100 g. These results indicate that calculating NPS per serving size allows for the assessment of the nutritional value of food items in accordance with actual consumption quantities. Therefore, the Meiji NPS calculated per serving size, alongside the per 100 g version, may be useful for dietary management depending on specific purposes.

In 2004, the equine-origin H3N8 canine influenza virus (CIV) first caused an outbreak with lethal cases in racing greyhounds in Florida, USA, and then spread to domestic dogs nationwide. Although transmission of this canine virus to humans has not been reported, it is important to evaluate its zoonotic potential because of the high contact opportunities between companion dogs and humans. To gain insight into the interspecies transmissibility of H3N8 CIV, we tested its adaptability to human respiratory A549 cells through successive passages. We found that CIV acquired high growth properties in these cells mainly through mutations in surface glycoproteins, such as hemagglutinin (HA) and neuraminidase (NA). Our reverse genetics approach revealed that HA2-K82E, HA2-R163K, and NA-S18L mutations were responsible for the increased growth of CIV in human cells. Molecular analyses revealed that both HA2 mutations altered the optimum pH for HA membrane fusion activity and that the NA mutation changed the HA-NA functional balance. These findings suggest that H3N8 CIV could evolve into a human pathogen with pandemic potential through a small number of mutations, thereby posing a threat to public health in the future., (© 2024. The Author(s).)

Background: Nutritional profiling system (NPS) holds promise as a public health tool for companies to measure product healthiness and for individuals in making healthier food choices. The Meiji NPS for adults specifically targets lifestyle-related diseases prevalent among Japan's adult population, including overweight/obesity, hypertension, diabetes, and dyslipidemia. This study examined the cross-sectional association between the Meiji NPS for adults Dietary Index (MNfA-DI) and indicators of lifestyle-related diseases in a population., Methods: The study comprised 1,272 middle-aged individuals (40-64 years, 50.1% male) who participated in the seventh wave (2010-2012) of the National Institute for Longevity Sciences-Longitudinal Study of Aging project, with no missing data on three-day dietary records. The MNfA-DI was computed at the individual diet level (accounting for the whole diet) using arithmetic energy-weighted means. A higher MNfA-DI indicated a greater nutritional quality of an individual's overall diet. Lifestyle-related disease indicators included body mass index (BMI, kg/m 2 ), body fat (%), systolic and diastolic blood pressure (mmHg), fasting plasma glucose (mg/dL), HbA1c (%), triglyceride levels (mg/dL), LDL, and HDL cholesterol levels (mg/dL). A multiple regression model was used to assess the association between the MNfA-DI and lifestyle-related disease indicators, adjusting for demographics, socioeconomic status, lifestyle factors, disease history, and energy intake as covariates, depending on the outcome., Results: The median (interquartile range) age and MNfA-DI were 53.0 (46.0, 59.0) years and 10.1 (6.0, 14.0) points, respectively. MNfA-DI was negatively associated with body fat [partial regression coefficient (95% confidence interval) -0.04 (-0.07, -0.01)], diastolic blood pressure [-0.08 (-0.17, -0.002)], fasting plasma glucose [-0.18 (-0.33, -0.01)], and triglyceride [-1.36 (-2.16, -0.55)]. Additionally, MNfA-DI was also associated with almost indicators (except for LDL and HDL cholesterol) among participants with a BMI between 18.5 and 24.9 kg/m 2 ., Conclusion: These findings suggest that the Meiji NPS for adults could be associated with a lower risk of lifestyle-related diseases. In addition, from a public health nutrition perspective, the Meiji NPS for adults may be useful to assess the food healthiness of the adult population., Competing Interests: TY, RW, and TH are full-time employees of R&D Division Meiji Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yu, Zhang, Wakayama, Horimoto, Tange, Nishita and Otsuka.)

The Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, has a wide host range, extending from pigs and ardeid birds to opportunistic dead-end hosts, such as humans and horses. However, JEV encephalitis infections in aquatic mammals are rare, with only two cases in seals reported to date. Here, we report a lethal case of JEV and Schizophyllum commune co-infection in an aquarium-housed harbor seal in Japan. We isolated JEV from the brain of the dead seal and characterized its phylogeny and pathogenicity in mice. The virus isolate from the seal was classified as genotype GIb, which aligns with recent Japanese human and mosquito isolates as well as other seal viruses detected in China and Korea, and does not exhibit a unique sequence trait distinct from that of human and mosquito strains. We demonstrated that the seal isolate is pathogenic to mice and causes neuronal symptoms. These data suggest that seals should be considered a susceptible dead-end host for circulating JEV in natural settings.

Utilities of whey powder (WP) and whey protein concentrate 34% powder (WPC34) prepared as dairy-processing residues were evaluated using a green alga Chlamydomonas reinhardtii . Analysis of C. reinhardtii growth showed that the strain used WP and WPC34 as nitrogen sources. Its specific growth rate and maximum cell density in WP-containing medium were higher than those in WPC34-containing medium; growth with WPC34 was improved by adding KCl or K 2 HPO 4 , which content was decreased as a result of WPC34's preparation from WP. Although the lipid contents in media containing dairy-processing residues were 2.72 ± 0.31 wt% and 2.62 ± 0.20 wt% with no significant difference, the composition ratio of fatty acid C14 with WPC34 was higher than that with WP and the composition ratio of the sum of fatty acid-C16 and -C18 with WPC34 tended to be lower than that with WP. Additionally, analyses of gene transcription showed that the transcription level of acetyl-CoA carboxylase biotin carboxyl carrier protein in WPC34-containing medium was lower than that in WP-containing medium, possibly affecting the ratios of the chain lengths of fatty acids. The transcription of genes involved in glycolysis and the TCA cycle was outstandingly lower in algae grown in WPC34-containing medium when compared to those cultivated in the presence of WP, resulting in differences in energy production for cell proliferation.

This study introduces the Meiji Nutritional Profiling System (Meiji NPS), which was specifically designed to respond to age-related shifts in nutrient requirements among Japanese adults (<65 years old) and older adults (≥65 years old). Japan has one of the most aged societies in the world. The health issues of interest are malnutrition and lifestyle-related diseases among adults and frailty among older adults. Two versions of the NPS were developed based on nutrients to encourage (protein, dietary fibers, calcium, iron, and vitamin D), food groups to encourage (fruits, vegetables, nuts, legumes, and dairy), and nutrients to limit (energy, saturated fatty acids, sugars, and salt equivalents). The Meiji NPS for older adults did not include iron or saturated fatty acids. The algorithms were based on the Nutrient-Rich Foods Index (NRF). The convergent validity between the Meiji NPS and the existing NPSs for the same foods was confirmed using Spearman's correlation coefficients (NRF: r = 0.67 for adults and r = 0.60 for older adults; Health Star Rating: r = 0.64 for adults and r = 0.61 for older adults). The Meiji NPS may be useful for nutritional evaluation and reformulation of food products, tailored to adults and older adults to ameliorate health issues in Japan.

Influenza D virus (IDV) is one of the causative agents of bovine respiratory disease complex, which is the most common and economically burdensome disease affecting the cattle industry, and the need for an IDV vaccine has been proposed to enhance disease control. IDVs are classified into five genetic lineages based on the coding sequences of the hemagglutinin-esterase-fusion (HEF) protein, an envelope glycoprotein, which is the main target of protective antibodies against IDV infection. Herein, we prepared a panel of monoclonal antibodies (mAbs) against the HEF protein of viruses of various lineages to investigate the antigenic characteristics of IDVs and found that the mAbs could be largely separated into three groups. The first, second, and third groups demonstrated lineage-specific reactivity, cross-reactivity to viruses of multiple but not all lineages, and cross-reactivity to viruses of all lineages, respectively. Analyzing the escape mutant viruses from virus-neutralizing mAbs revealed that the receptor-binding region of the HEF molecule harbors virus-neutralizing epitopes that are conserved across multiple lineage viruses. In contrast, the apex region of the molecule possessed epitopes unique to each lineage virus. Furthermore, reverse genetics-generated recombinant viruses with point mutations revealed that amino acids within positions 210-214 of the HEF protein determined the antigenic specificity of each lineage virus. Taken together, this study reveals considerable antigenic variation among IDV lineages, although they are presumed to form a single serotype in terms of HEF antigenicity. Characterization of the antigenic epitope structure of HEF may contribute to selecting and creating effective vaccine viruses against IDV.IMPORTANCEInfluenza D viruses (IDVs) are suggested to create cross-reactive single serotypes in hemagglutinin-esterase-fusion (HEF) antigenicity, as indicated by serological analyses among distinct HEF lineage viruses. This is supported by the high identities of HEF gene sequences among strains, unlike the hemagglutinin (HA) genes of the influenza A virus that exhibit HA subtypes. Herein, we analyzed HEF antigenicity using a monoclonal antibody panel prepared from several virus lineages and found the existence of lineage-conserved and lineage-specific epitopes in HEF molecules. These findings confirm the HEF commonality and divergence among IDVs and provide useful information for constructing a vaccine containing a recombinant IDV virus with an engineered HEF gene, thereby leading to broad immunogenicity., Competing Interests: The authors declare no conflict of interest.

Akabane virus (AKAV) is a member of the genus Orthobunyavirus, family Peribunyaviridae. In addition to AKAV strains that cause fetal Akabane disease, which is characterized by abortion in ruminants, some AKAV strains cause postnatal infection characterized by nonsuppurative encephalomyelitis in ruminants. Here, we focused on the NSs protein, a virulence factor for most viruses belonging to the genus Orthobunyavirus, and we hypothesized that this protein would act as a neurovirulence factor in AKAV strains causing postnatal encephalomyelitis. We generated AKAV strains that were unable to produce the NSs protein, derived from two different genogroups, genogroups I and II, and then examined the role of their NSs proteins by inoculating mice intracerebrally with these modified viruses. Our results revealed that the neurovirulence of genogroup II strains is dependent on the NSs protein, whereas that of genogroup I strains is independent of this protein. Notably, infection of primary cultured bovine cells with these viruses suggested that the NSs proteins of both genogroups suppress innate immune-related gene expression with equal efficiency. These results indicate differences in the determinants of virulence of orthobunyaviruses., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Ageing limits the activities of daily living (ADLs). Among ADLs, a lack of toileting independence causes a decline in the quality of life, mental health, and social participation. Therefore, occupational therapists spend considerable time assessing toileting disability based on various assessment methods for toileting behaviour. However, these assessment methods have issues with the grading levels, number of items, and diseases covered, and they fail to evaluate toileting behaviour accurately and sensitively. Hence, this study developed a Toileting Behaviour Evaluation (TBE) on a 6-point ordinal scale for patients using wheelchairs, with 22 activity components for various diseases., Methods: This study examined the reliability and validity of the TBE in acute and subacute hospitals in Japan. To this end, two occupational therapists assessed 50 patients for inter-rater reliability at different times and one assessed them twice within 7-10 days for intra-rater reliability using the TBE. Furthermore, occupational therapists assessed 100 patients for internal consistency using the TBE and for concurrent validity using the TBE and Functional Independence Measure (FIM). The patients had been diagnosed with various diseases. This study used the weighted kappa coefficient for statistical analysis of the inter-rater and intra-rater reliability, Cronbach's alpha coefficient for internal consistency, and Spearman's rank correlation coefficient for concurrent validity. We performed all statistical analyses using the IBM SPSS Statistics ver. 25 for Windows. All P-values < 0.05 were considered statistically significant., Results: The minimum weighted kappa coefficients for the inter-rater and intra-rater reliability for each item were 0.67 and 0.79, respectively. Cronbach's alpha was 0.98 for the 22 items. The Spearman's rank correlation coefficient between the mean scores on the TBE and FIM for toilet-related items was 0.74 (P < .01)., Conclusions: The TBE demonstrated good reliability and validity. This means that therapists can use it to identify impaired toileting behaviour. However, the relationship between impairments and each item of toileting behaviour should be explored in future studies. Additionally, studies should examine the creation of a specific index of functions of independence in each toileting behaviour., (© 2023. The Author(s).)

Throughout East Asia, Europe, and North America, mammalian orthoreovirus (MRV), for which bats have been proposed to be natural reservoirs, has been detected in a variety of domestic and wild mammals, as well as in humans. Here, we isolated a novel MRV strain (designated as Kj22-33) from a fecal sample from Vespertilio sinensis bats in Japan. Strain Kj22-33 has a 10-segmented genome with a total length of 23,580 base pairs. Phylogenetic analysis indicated that Kj22-33 is a serotype 2 strain, the segmented genome of which has undergone reassortment with that of other MRV strains., (© 2023. The Author(s).)

Influenza D virus (IDV) is a causative agent of the bovine respiratory disease complex (BRDC), which is the most common and costly disease affecting the cattle industry. For developing a candidate vaccine virus against IDV, we sought to produce a temperature-sensitive strain, similar to the live attenuated, cold-adapted vaccine strain available against the influenza A virus (IAV). To this end, we produced a recombinant IDV (designated rD/OK-AL) strain by introducing mutations responsible for the adaptation of the IAV vaccine strain to cold conditions and conferring sensitivity to high temperatures into PB2 and PB1 proteins using reverse genetics. The rD/OK-AL strain grew efficiently at 33 °C but did not grow at 37 °C in the cell culture, indicating its high-temperature sensitivity. In mice, rD/OK-AL was attenuated following intranasal inoculation. It mediated the production of high levels of antibodies against IDV in the serum. When the rD/OK-AL-inoculated mice were challenged with the wild-type virus, the virus was not detected in respiratory organs after the challenge, indicating complete protection against IDV. These results imply that the rD/OK-AL might be a potential candidate for the development of live attenuated vaccines for IDV that can be used to control BRDC., (© 2023. The Author(s).)

Canine adenoviruses (CAdVs) are divided into two serotypes, CAdV1 and CAdV2, whose members mainly cause infectious hepatitis and laryngotracheitis, respectively, in canids. To gain insight into the molecular basis of viral hemagglutination, we constructed chimeric viruses whose fiber proteins or their knob domains, which play a role in viral attachment to cells, were swapped among CAdV1, CAdV2, and bat adenovirus via reverse genetics. The results revealed that, in each case, viral hemagglutination was specifically mediated by the fiber protein or knob domain, providing direct evidence for fiber-protein-directed receptor-binding characteristics of CAdVs., (© 2023. The Author(s).)

The emergence and spread of antiviral-resistant influenza viruses are of great concern. To minimize the public health risk, it is important to monitor antiviral susceptibilities of influenza viruses. Analyses of the antiviral susceptibilities of influenza A and B viruses have been conducted globally; however, those of influenza C and D viruses are limited. Here, we determined the susceptibilities of influenza C viruses representing all six lineages (C/Taylor, C/Yamagata, C/Sao Paulo, C/Aichi, C/Kanagawa, and C/Mississippi) and influenza D viruses representing four lineages (D/OK, D/660, D/Yama2016, and D/Yama2019) to RNA polymerase inhibitors (baloxavir and favipiravir) by using a focus reduction assay. All viruses tested were susceptible to both drugs. We then performed a genetic analysis to check for amino acid substitutions associated with baloxavir and favipiravir resistance and found that none of the viruses tested possessed these substitutions. Use of the focus reduction assay with the genotypic assay has proven valuable for monitoring the antiviral susceptibilities of influenza C and D viruses as well as influenza A and B viruses. Antiviral susceptibility monitoring of all influenza virus types should continue in order to assess the public health risks posed by these viruses.

Surveillance of bat betacoronaviruses is crucial for understanding their spillover potential. We isolated bat sarbecoviruses from Rhinolophus cornutus bats in multiple locations in Japan. These viruses grew efficiently in cells expressing R. cornutus angiotensin converting enzyme-2, but not in cells expressing human angiotensin converting enzyme-2, suggesting a narrow host range.

Betacoronaviruses, containing sarbecoviruses such as severe acute respiratory syndrome coronaviruses (SARS-CoV) and merbecovirus such as Middle East respiratory syndrome coronavirus (MERS-CoV), caused three human outbreaks in the past 2 decades; in particular, SARS-CoV-2 has caused the coronavirus disease 2019 pandemic. Since the ancestor of betacoronaviruses originated from wild bats, unidentified bat betacoronaviruses are presumed to be transmitted to humans in the future. In this study, we detected novel bat merbecoviruses from Vespertilio sinensis and Eptesicus japonensis, belonging to the family Vespertilionidae, in Japan. We found that these merbecoviruses were phylogenetically most closely related to the those previously detected in China. Alignment of the predicted receptor-binding motif on the spike proteins indicated that the Japanese bat merbecoviruses did not possess the specific amino acid residues that could be responsible for binding of MERS-CoV to the human dipeptidyl peptidase-4 receptor, which is unlikely to infect humans. This study demonstrated that bat merbecoviruses are widely conserved in multiple bat species of Vespertilionidae in East Asia, emphasizing the need for extensive epidemiological and biological studies on bat betacoronaviruses to facilitate the risk assessment of their spillover potential to humans., (© 2022 Wiley-VCH GmbH.)

Avian or human influenza A viruses bind preferentially to avian- or human-type sialic acid receptors, respectively, indicating that receptor tropism is an important factor for determining the viral host range. However, there are currently no reliable methods for analyzing receptor tropism biologically under physiological conditions. In this study, we established a novel system using MDCK cells with avian- or human-type sialic acid receptors and with both sialic acid receptors knocked out (KO). When we examined the replication of human and avian influenza viruses in these KO cells, we observed unique viral receptor tropism that could not be detected using a conventional solid-phase sialylglycan binding assay, which directly assesses physical binding between the virus and sialic acids. Furthermore, we serially passaged an engineered avian-derived H4N5 influenza virus, whose PB2 gene was deleted, in avian-type receptor KO cells stably expressing PB2 to select a mutant with enhanced replication in KO cells; however, its binding to human-type sialylglycan was undetectable using the solid-phase binding assay. These data indicate that a panel of sialic acid receptor KO cells could be a useful tool for determining the biological receptor tropism of influenza A viruses. Moreover, the PB2KO virus experimental system could help to safely and efficiently identify the mutations required for avian influenza viruses to adapt to human cells that could trigger a new influenza pandemic. IMPORTANCE The acquisition of mutations that allow avian influenza A virus hemagglutinins to recognize human-type receptors is mandatory for the transmission of avian viruses to humans, which could lead to a pandemic. In this study, we established a novel system using a set of genetically engineered MDCK cells with knocked out sialic acid receptors to biologically evaluate the receptor tropism for influenza A viruses. Using this system, we observed unique receptor tropism in several virus strains that was undetectable using conventional solid-phase binding assays that measure physical binding between the virus and artificially synthesized sialylglycans. This study contributes to elucidation of the relationship between the physical binding of virus and receptor and viral infectivity. Furthermore, the system using sialic acid knockout cells could provide a useful tool to explore the sialic acid-independent entry mechanism. In addition, our system could be safely used to identify mutations that could acquire human-type receptor tropism.

The mottled skate Beringraja pulchra is a coastal fish caught by gillnet and bottom trawl fisheries in Hokkaido, Japan. We recently found a parasitic copepod identical to Pseudocharopinus markewitschi (Gusev, 1951) on this commercially important fish. A total of 109 host individuals caught off the coast of northern Hokkaido, Japan, were examined for adult females of this copepod, and 67 cases (61.5%) of infection comprised with 31 cases (67.4%) of 46 males and 36 cases (57.1%) of 63 females were found. The parasite specimens (n = 229) were recovered mainly from the dorsal side of the pelvic fin (n = 168, 73.4%), followed by the claspers (n = 32, 14.0%). The mottled skate is thought to spend most of its lifetime lying in sand or crawling on the seafloor. Therefore, the biased infection to the dorsal side of the pelvic fin may imply that site selection favors less susceptible for disturbances resulting from such host-specific behavior., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Akabane virus (AKAV) is an etiological agent that is teratogenic to the fetus of domestic ruminants, causing a significant loss of reproduction in livestock. In East Asia, AKAV isolates form two major clusters: genogroups I and II. In recent years, genogroup I isolates have also been associated with postnatal encephalomyelitis, mainly in calves. Here, we compared the pathogenicity in mice using genogroup I Iriki and genogroup II OBE-1 strains. Only mice infected intraperitoneally with the Iriki strain died and showed marked replication in the central nervous system (CNS) and lymphoid tissues. A more elevated blood-brain barrier (BBB) permeability was found in the Iriki-infected mice in the clinical phase, indicating that the BBB might be a possible route of viral transmission from the periphery to the CNS. These findings demonstrate that the Iriki strain presents greater neurovirulence and neuroinvasiveness compared with the OBE-1 strain, determining different AKAV pathogenicity among genogroups., (Copyright © 2022. Published by Elsevier B.V.)

Ferrets are animals that are known to be susceptible to influenza A virus (IAV) infection. To evaluate the risk of IAV transmission from diseased ferrets to humans, a survey was performed to detect specific antibodies against the H1, H3, H5, and H7 subtypes of IAV. Using enzyme-linked immunosorbent assay for hemagglutinin proteins, we found a high positive rate for the H1 (24.1%) and H3 (5.2%) subtypes. The results were confirmed by a virus neutralization test for representative antibody-positive serum samples. We also detected hemagglutinin and neuraminidase genes in two ferrets showing acute respiratory disease and whose owner was diagnosed with IAV infection; a human H1N1pdm virus was isolated from one of these ferrets. Our findings suggest that attention should be paid to IAV infection from humans to ferrets and vice versa.

During 2016-2017, the H7N2 feline influenza virus infected more than 500 cats in animal shelters in New York, USA. A veterinarian who had treated the cats became infected with this feline virus and showed mild respiratory symptoms. This suggests that the H7N2 feline influenza virus may evolve into a novel pandemic virus with a high pathogenicity and transmissibility as a result of mutations in humans. In this study, to gain insight into the molecular basis of the transmission of the feline virus to humans, we selected mutant viruses with enhanced growth in human respiratory A549 cells via successive passages of the virus and found almost all mutations to be in the envelope glycoproteins, such as hemagglutinin (HA) and neuraminidase (NA). The reverse genetics approach revealed that the HA mutations, HA1-H16Q, HA2-I47T, or HA2-Y119H, in the stalk region can lead to a high growth of mutant viruses in A549 cells, possibly by changing the pH threshold for membrane fusion. Furthermore, NA mutation, I28S/L, or three-amino-acid deletion in the transmembrane region can enhance viral growth in A549 cells, possibly by changing the HA-NA functional balance. These findings suggest that the H7N2 feline influenza virus has the potential to become a human pathogen by adapting to human respiratory cells, owing to the synergistic biological effect of the mutations in its envelope glycoproteins.

Here, we report a novel bat adenovirus strain isolated from apparently healthy bats of the species Rhinolophus cornutus in Japan. The genome of the isolate was 36,506 bp in length and encoded at least 33 proteins. Phylogenetic analysis of the DNA polymerase amino acid sequence, which provides one demarcation criterion for adenoviral species, indicated that the isolate belongs to the species Bat mastadenovirus C in the genus Mastadenovirus. Most of the encoded proteins shared high sequence similarity with those of known bat adenovirus C strains detected in different species of Rhinolophus, whereas the fiber protein and some E3- and E4-related proteins shared moderate similarity, and only the large E3 protein, which contains several host immune-suppression-related motifs, showed considerably lower similarity., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Influenza D virus (IDV) may cause the bovine respiratory disease complex, which is the most common and costly disease affecting the cattle industry. Previously, we revealed that eight segments could be actively packaged in its single virion, suggesting that IDV with the seven-segmented genome shows an agnostic genome packaging mechanism. Herein, we engineered an eight-segmented recombinant IDV in which the NS1 or NS2 genes were separated from NS segment into independent segments (NS1 or NS2 segments, respectively), leading to monocistronic translation of each NS protein. We constructed two plasmids: one for the viral RNA (vRNA)-synthesis of the NS1 segment with a silent mutation at the splicing acceptor site, which controls NS2 transcription in the NS segment; and another for the RNA synthesis of the NS2 segment, with deletion of the intron in the NS segment. These plasmids and six other vRNA-synthesis plasmids were used to fabricate an infectious eight-segmented IDV via reverse genetics. This system enables analysis of the functions of NS1 or NS2. We tested the requirement of the N-terminal overlapping region (NOR) in these proteins for viral infectivity. We rescued a virus with NOR-deleted NS2 protein, which displayed a growth rate equivalent to that of the eight-segmented virus with intact NS2. Thus, the NOR may not influence viral growth. In contrast, a virus with NOR-deleted NS1 protein could not be rescued. These results indicate that the eight-segmented rescue system of IDV may provide an alternative method to analyze viral proteins at the molecular level.

Although a canine adenovirus (CAdV)-based oncolytic virus (OV) candidate targeting canine tumors has been reported, its oncolytic effect could be attenuated by CAdV vaccine-induced neutralizing antibodies in dog patients. To circumvent this issue, we focused on the bat adenovirus (BtAdV) strain, which was previously isolated from healthy microbats. We previously showed that this virus replicated efficiently in canine cell lines and did not serologically cross-react with CAdVs, suggesting that it may offer the possibility of an OV candidate for canine tumors. Here, we tested the growth properties and cytotoxicity of the BtAdV Mm32 strain in a panel of canine tumor cells and found that its characteristics were equivalent to those of CAdVs. To produce an Mm32 construct with enhanced tumor specificity, we established a novel reverse genetics system for BtAdV based on bacterial artificial chromosomes, and generated a recombinant virus, Mm32-E1Ap + cTERTp, by inserting a tumor-specific canine telomerase reverse transcriptase promoter into its E1A regulatory region. The growth and cytotoxicity of this recombinant were superior to those of wild-type Mm32 in canine tumor cells, unlike in normal canine cells. These data suggest that Mm32-E1Ap + cTERTp could be a promising OV for alternative canine cancer therapies., (© 2021. The Author(s).)