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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing novel coronavirus disease 2019 (COVID-19) appeared in Wuhan, Hubei province, China in late December 2019 and has rapidly spread worldwide. In this study, a total of 267 genomes of SARS CoV-2 viruses collected from 28 Center for Diseases Controls and hospitals in different provinces in Northern and Central Vietnam from January 2020 to April 2021 were sequenced and analyzed their diversity using the iSeq 100 platform. Results showed that most of the virus samples originated from domestic community patients (84.3%). Variable variants of SARS CoV-2 virus were detected within the three pandemic waves. The very first variant of SARS-CoV-2 in Viet Nam in January 2020 was 19B (Nextstrain Clade), 3/8 of the variants were from the international arrival samples group. In the first and second pandemic waves, lineage 20B was the most prevalent and this variant was found in Da Nang, Hai Duong and Thai Binh with a large number of patients. In the third wave of the COVID-19 pandemic, lineage 20I was the most dominant and detected in all provinces where the outbreak occurred. Five COVID-19 clusters caused by SARS-CoV-2 variant 20I were also found during this time.

Hamster polyomavirus (HaPyV) infection has been associated with lymphomas in Syrian hamsters. In the present study, 14 cases of lymphoma in pet Syrian hamsters were pathologically examined and the involvement of HaPyV was investigated. Among 14 cases, 11 were abdominal and 3 were cutaneous lymphomas. The average ages of hamsters with abdominal lymphoma and cutaneous lymphoma were 7 months (range: 4-12 months) and 14 months (range: 6-23 months), respectively. Histologically, abdominal lymphomas were characterized by the diffuse growth of tumor cells with intermediate or large nuclei, low mitotic rates, the presence of tingible body macrophages, and the T-cell immunophenotype. Furthermore, 4/11 abdominal lymphomas were immunopositive for T-cell intracellular antigen-1, suggesting cytotoxic T-cell lymphomas. Cutaneous lymphomas were diagnosed as nonepitheliotropic T-cell lymphoma. Polymerase chain reaction (PCR) detected HaPyV DNA in 12/14 samples, and a sequence analysis of PCR amplicons confirmed >99% nucleotide identity to the published HaPyV sequences. In situ hybridization (ISH) for HaPyV DNA resulted in diffuse nuclear signals within tumor cells in 10/14 cases. Consistent with previous findings, all HaPyV-associated lymphomas were observed in the abdominal cavity of young hamsters. Polymerase chain reaction and ISH were useful for identifying the involvement of HaPyV in lymphomas, and ISH results indicated the presence of episomal HaPyV in neoplastic lymphocytes. The present study suggests that HaPyV infection is highly involved in abdominal lymphomas in young pet Syrian hamsters in Japan and provides diagnostic information on HaPyV-associated lymphoma.

From January to August 2020, Northern Viet Nam faced a COVID-19 outbreak, up to September 2020, there were 1122 confrmed cases of SARS-CoV-2, of which 465 cases were imported from Europe, America and Asia, 657 cases were identifed domestically. A total of 30,686 samples were collected during the SARS-CoV-2 outbreak in Northern Viet Nam and examined by Real-time RT-PCR using primers and probe from Charite - Berlin protocol. This study showed the initial results of SARS-CoV-2 detection and RNA quantitative in positive samples. The positive rate was 0.8%, ranging from 0.4 to 3.5% according to collection sites. Out of 251 positive samples, the mean Ct value was 28 (IQR: 22.3-32; range 14 - 38). The positive samples had a Ct value below 30 was 68.5%, there was no signifcant difference between the Ct value of the group ≤ 30 and > 30. The mean of the RNA copies/µl was 8.4.107, (IQR: 2.29.106 - 1.83.109 RNA copies/µl, range: 1.95.103 – 4.95.1011). In the group of imported COVID-19 cases, the rate of virus at low level was 29%, an average was 56% and at high level was 15%. In the community groups, the viral load data showed that the average rate at low, intermediate and high level were 20%, 63% and 17% respectively. The proportion of high-level viral load may raise an alert to start the quarantine process to reduce the transmission of SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was appeared in Wuhan, Hubei province, Chinain late December 2019. Rapidly, COVID-19 (disease caused by SARS-CoV-2) then spread rapidly to more than 200countries and regions around the world in April 2020. Since Vietnam is one of the frst countries to detect COVID-19patients, diagnostic methods and outbreak management are essentially needed for the national guidelines. The NationalInstitute of Hygiene and Epidemiology (NIHE) decided to conduct a study by collecting nasal swab from suspectedpeoples. These specimens were screened and inoculated the positive specimens. From January to August 2020, 40 positive specimens of clinical symptoms which Ct < 30 and 27 isolated specimens were sequencing. All the specimens weresequenced the frst time on the Illumina iSeq 100 platform in Vietnam. After 15 operations (12 complete and othersincomplete ones), the entire genome virus of 27 viral strains and 12 clinical specimens were listed. Based on GISAID,these sequences were grouped into three big groups (S, V, G) with dominance of subclade GR (17 isolates and 9 clinicalsamples). Eight isolated sequences were uploaded to Genbank to share data with other researchers in worldwide.

A cluster of severe acute respiratory syndrome coronavirus 2 infections in Danang, Vietnam, began July 25, 2020, and resulted in 551 confirmed cases and 35 deaths as of February 2021. We analyzed 26 sequences from this cluster and identified a novel shared mutation in nonstructural protein 9, suggesting a single introduction into Vietnam.

This report described the histopathological and immunohistochemical features of cutaneous mast cell tumor (MCT) in six hedgehogs. The hedgehogs presented single cutaneous mass with ulcer and crusting. Histologically, the neoplastic lesions were characterized by the proliferation of well-differentiated mast cells (3 cases), and atypical mast cells (3 cases) with one atypical histiocytic morphology. Immunohistochemically, tumor cells were positive for KIT and mast cell tryptase, and were negative for Iba-1. In well-differentiated MCT, all patients were clinically improved and survived more than 365 days after surgical excision, whereas an atypical histiocytic MCT showed aggressive behavior with re-recurrence, and the animal died 115 days after surgery. These findings suggest that, compatible with other animals, well-differentiated MCT has a better prognosis in hedgehogs.

Respiratory syncytial virus (RSV) is one of the most interesting respiratory viruses in the world. This virus causes symptoms of illnesses like influenza and imposes a heavy burden on medical services and the economy. However, studies on RSV in Vietnam are limited, while most of the RSV research has primarily been done before 2015. We collected the clinical respiratory samples from severe acute respiratory infection (SARI) patients to screen for RSV by real-time RT-PCR and study their molecular characteristics. RSV-positive specimens with Ct value < 25 collected between 2017-2018 in north Vietnam were inoculated on the Hep2 cell line. The results showed that 25 (22.32%) RSV virus strains were harvested from the inoculation procedure with 18 RSV A and 7 RSV B. The whole genomes of four representative strains were sequenced with the Illumina iSeq 100. Phylogenetic trees analysis of each subtype were classified as two RSV A and two RSV B sequences as genotype ON1 lineage 1.2 and genotype BA9 respectively. These genotypes were identified as typical Vietnamese strains from 2009-2012. Nevertheless, the RSV strains before 2015 and those in this study had significant differences in the G gene, with 34–35 amino acids in RSV A and 4 amino acids in RSV B. Moreover, the first whole genome of Vietnamese RSV since 2016 may give more understanding of the molecular characteristics of RSVs in Vietnam.

学位の種別: 課程博士, 審査委員会委員 : （主査）東京大学教授 中山 裕之, 東京大学教授 辻本 元, 東京大学准教授 中川 貴之, 東京大学准教授 米澤 智洋, 東京大学准教授 内田 和幸

Influenza B viruses circulate throughout Viet Nam, and their activities vary by region. There have been two antigenically distinct lineages of influenza B viruses co-circulating in the past 20 years; however, only one lineage is selected as a component of contemporary trivalent seasonal influenza vaccines. To improve the understanding of circulating influenza B lineages and influenza vaccine mismatches, we report the virus lineages circulating in northern Viet Nam over an eight-year period (2007-2014).Lineages of 331 influenza B viruses were characterized by haemagglutination inhibition assay against standard reference ferret (Yamagata) and sheep (Victoria) antisera. Sequence analysis of the haemagglutinin gene was performed in 64 selected influenza B isolates.The proportion of influenza B lineages changed by year. The Yamagata lineage predominated in 2007, 2008 and 2012; the Victoria lineage predominated in 2009-2014 except 2012. The two lineages showed continuous evolution over time. The Northern Hemisphere's influenza vaccine components were mismatched with the predominant circulating viruses in 2007, 2009 and 2014.The seasonality of influenza B activity is more variable in tropical and subtropical regions than in temperate zones. Our data showed a common co-circulation of both influenza B lineages in northern Viet Nam, and it was difficult to predict which one was the predominant lineage. Quadrivalent influenza vaccines containing both lineages may improve the effectiveness of influenza vaccine programmes in the future.

In this paper, the secure communication system is presented in which projective-lag synchronization of multidelay Mackey-Glass systems with mulitidelay driving signal and the modulation scheme of synchronization-manifold shift keying (SMSK) are utilized. Moreover, the methods to enhance the security are considered. The effectiveness of the proposed model is demonstrated and verified by the specific examples with five-delay Mackey-Glass systems.