Publications by authors named "Kazushi Motomura"

48 Publications

Full genome-based characterization of G4P[6] rotavirus strains from diarrheic patients in Thailand: Evidence for independent porcine-to-human interspecies transmission events.

Virus Genes 2021 Jun 9. Epub 2021 Jun 9.

Department of Virology and Parasitology, Fujita Health University School of Medicine, Toyoake, Aichi, 470-1192, Japan.

The exact evolutionary patterns of human G4P[6] rotavirus strains remain to be elucidated. Such strains possess unique and strain-specific genotype constellations, raising the question of whether G4P[6] strains are primarily transmitted via independent interspecies transmission or human-to-human transmission after interspecies transmission. Two G4P[6] rotavirus strains were identified in fecal specimens from hospitalized patients with severe diarrhea in Thailand, namely, DU2014-259 (RVA/Human-wt/THA/DU2014-259/2014/G4P[6]) and PK2015-1-0001 (RVA/Human-wt/THA/PK2015-1-0001/2015/G4P[6]). Here, we analyzed the full genomes of the two human G4P[6] strains, which provided the opportunity to study and confirm their evolutionary origin. On whole genome analysis, both strains exhibited a unique Wa-like genotype constellation of G4-P[6]-I1-R1-C1-M1-A8-N1-T1-E1-H1. The NSP1 genotype A8 is commonly found in porcine rotavirus strains. Furthermore, on phylogenetic analysis, each of the 11 genes of strains DU2014-259 and PK2015-1-0001 appeared to be of porcine origin. On the other hand, the two study strains consistently formed distinct clusters for nine of the 11 gene segments (VP4, VP6, VP1-VP3, and NSP2-NSP5), strongly indicating the occurrence of independent porcine-to-human interspecies transmission events. Our observations provide important insights into the origin of zoonotic G4P[6] strains, and into the dynamic interaction between porcine and human rotavirus strains.
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http://dx.doi.org/10.1007/s11262-021-01851-yDOI Listing
June 2021

Relationship between biochemical markers and measles viral load in patients with immunologically naive cases and secondary vaccine failure -LDH is one of the potential auxiliary indicators for secondary vaccine failure.

Microbiol Immunol 2021 May 5. Epub 2021 May 5.

Osaka Institute of Public Health, 3-69, Nakamichi, 1-chome, Higashinari-ku, Osaka, 537-0025, Japan.

This study investigated the correlation between biochemical markers and viral load among 38 measles cases, including 15 immunologically naive patients and 23 patients with secondary vaccine failure (SVF). We examined four biochemical markers, namely, aspartate aminotransferase, alanine aminotransferase, C-reactive protein, and lactate dehydrogenase (LDH) and their relationship between virus genome copy numbers in peripheral blood mononuclear cells (PBMCs) and throat swabs as well as the concentration of measles-specific IgG. Although viral genome copies in both clinical specimens showed a significant correlation with specific IgG concentration, they had a higher correlation in PBMCs (Pearson's product-moment correlation coefficient, -0.662; p < 0.0001) than in throat swabs (Spearman's rank correlation coefficient, -0.443; p = 0.0078). The viral load in PBMCs also significantly correlated with LDH values (correlation coefficient, 0.360; p = 0.036). Thus, serum LDH level might be a potential auxiliary indicator to distinguish immunologically naive patients with measles from those with SVF. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/1348-0421.12891DOI Listing
May 2021

Seasonal shift in epidemics of respiratory syncytial virus infection in Japan.

Epidemiol Infect 2021 02 11;149:e55. Epub 2021 Feb 11.

Department of Public Health, Osaka Institute of Public Health, Osaka, Japan.

In Japan, respiratory syncytial virus (RSV) infection generally has occurred during autumn and winter. However, a possible change in the seasonal trend of RSV infection has been observed recently. The current study was conducted to determine whether the epidemic season of RSV infection in Japan has indeed changed significantly. We used expectation-based Poisson scan statistics to detect periods with high weekly reported RSV cases (epidemic cluster), and the epidemic clusters were detected between September and December in the 2012-2016 seasons while those were detected between July and October in the 2017-2019 seasons. Non-linear and linear ordinary least squares regression models were built to evaluate whether there is a difference in year trend in the epidemic seasonality, and the epidemic season was shifted to earlier in the year in 2017-2019 compared to that in 2012-2016. Although the reason for the shift is unclear, this information may help in clinical practice and public health.
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http://dx.doi.org/10.1017/S0950268821000340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060823PMC
February 2021

Two Different Strains of Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) in North and South Osaka by Phylogenetic Analysis of Evolutionary Lineage: Evidence for Independent SFTSV Transmission.

Viruses 2021 01 25;13(2). Epub 2021 Jan 25.

Virology Section, Division of Microbiology, Osaka Institute of Public Health, Osaka 537-0025, Japan.

Severe fever with thrombocytopenia syndrome (SFTS) is a novel tick-borne infectious disease, therefore, the information on the whole genome of the SFTS virus (SFTSV) is still limited. This study demonstrates a nearly whole genome of the SFTSV identified in Osaka in 2017 and 2018 by next-generation sequencing (NGS). The evolutionary lineage of two genotypes, C5 and J1, was identified in Osaka. The first case in Osaka belongs to suspect reassortment (L:C5, M:C5, S:C4), the other is genotype J1 (L: J1, M: J1, S: J1) according to the classification by a Japanese group. C5 was identified in China, indicating that C5 identified in this study may be transmitted by birds between China and Japan. This study revealed that different SFTSV genotypes were distributed in two local areas, suggesting the separate or focal transmission patterns in Osaka.
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http://dx.doi.org/10.3390/v13020177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911098PMC
January 2021

A measles outbreak in Kansai International Airport, Japan, 2016: Analysis of the quantitative difference and infectivity of measles virus between patients who are immunologically naive versus those with secondary vaccine failure.

J Med Virol 2021 06 29;93(6):3446-3454. Epub 2020 Dec 29.

Department of Health and Medical Care, Osaka Prefectural Government, Osaka, Japan.

Since the elimination of the measles virus, patients with vaccination records for the measles-containing vaccine have increased in Japan. According to several studies, the transmission risk from previously immunized patients, especially those with secondary vaccine failure (SVF), is lower than that from those with primary measles infections. Immunological features of SVF were identified per specific immunoglobulin G (IgG) induction with high avidity and high plaque reduction neutralization antibody concentration. However, the virological features of SVF have not been well investigated. To examine not only immunological but also virological differences between SVF and immunologically naive patients, throat swabs and blood and urine specimens of 25 patients with confirmed measles infection after an outbreak at the Kansai International Airport in 2016 were analyzed. Patients were categorized as naive (n = 3) or with SVF (n = 22) based on measles-specific IgG antibody concentrations and their avidity. Virus isolation and quantitative real-time polymerase chain reaction were performed to quantify the viral load in clinical specimens and estimate the infectivity in each specimen. The number of viral genome copies in the blood specimens of those with SVF was significantly different and approximately 1 out of 100 of that in immunologically naive patients. However, genome copy numbers in throat swabs and urine specimens were not significantly different between the groups. The virus was isolated only from those in the naive group. Our study indicated low transmission risk of the virus in patients with SVF.
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http://dx.doi.org/10.1002/jmv.26733DOI Listing
June 2021

Full genome characterization of novel DS-1-like G9P[8] rotavirus strains that have emerged in Thailand.

PLoS One 2020 22;15(4):e0231099. Epub 2020 Apr 22.

Department of Virology and Parasitology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.

The emergence and rapid spread of unusual DS-1-like intergenogroup reassortant rotaviruses having G1/3/8 genotypes have been recently reported from major parts of the world (Africa, Asia, Australia, Europe, and the Americas). During rotavirus surveillance in Thailand, three novel intergenogroup reassortant strains possessing the G9P[8] genotype (DBM2017-016, DBM2017-203, and DBM2018-291) were identified in three stool specimens from diarrheic children. In the present study, we determined and analyzed the full genomes of these three strains. On full-genomic analysis, all three strains were found to share a unique genotype constellation comprising both genogroup 1 and 2 genes: G9-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Phylogenetic analysis demonstrated that each of the 11 genes of the three strains was closely related to that of emerging DS-1-like intergenogroup reassortant, human, and/or locally circulating human strains. Thus, the three strains were suggested to be multiple reassortants that had acquired the G9-VP7 genes from co-circulating Wa-like G9P[8] rotaviruses in the genetic background of DS-1-like intergenogroup reassortant (likely equine-like G3P[8]) strains. To our knowledge, this is the first description of emerging DS-1-like intergenogroup reassortant strains having the G9P[8] genotype. Our observations will add to the growing insights into the dynamic evolution of emerging DS-1-like intergenogroup reassortant rotaviruses through reassortment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231099PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176146PMC
July 2020

Novel human reovirus isolated from children and its long-term circulation with reassortments.

Sci Rep 2020 01 22;10(1):963. Epub 2020 Jan 22.

Division of Public Health, Osaka Institute of Public Health, Osaka, 537-0025, Japan.

Mammalian orthoreovirus (MRV), also known as reovirus, was discovered in the 1950s and became the first reported segmented double-stranded RNA virus. MRVs have since been found in a variety of animal species, including humans. However, reports on MRV infections are scarce due to the rarity of their symptomatic occurrence. In Japanese surveillance studies, MRVs have been detected as gastrointestinal pathogens since 1981, with a total of 135 records. In Osaka City, Japan, MRV was first isolated in 1994 from a child with meningitis, and then in 2005 and 2014 from children with gastroenteritis. Here, we conducted the first molecular characterization of human MRV isolates from Japan and identified a novel human reovirus strain belonging to MRV type 2, designated the MRV-2 Osaka strain. This strain, with all three isolates classified, is closely related to MRV-2 isolates from sewage in Taiwan and is relatively close to an MRV-2 isolate from a bat in China. Our data suggest that the MRV-2 Osaka strain, which has circulated amongst humans in Japan for at least two decades, has spread internationally.
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http://dx.doi.org/10.1038/s41598-020-58003-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976588PMC
January 2020

A measles outbreak from an index case with immunologically confirmed secondary vaccine failure.

Vaccine 2020 02 9;38(6):1467-1475. Epub 2019 Dec 9.

Osaka Institute of Public Health, Morinomiya Center, 1-3-69, Nakamichi, Higashinari-ku, Osaka 537-0025, Japan. Electronic address:

During the elimination stage of measles, the development of such disease in individuals who received measles-containing vaccine (MCV) is a concern from an epidemiological standpoint. A few cases in which measles was transmitted from a patient who received two doses of MCV have been reported. However, whether such transmissions were caused by primary vaccine failure (PVF) or secondary vaccine failure (SVF) remains unclear. All patients suspected of measles in Osaka Prefecture between November and December 2018 were enrolled. Data about age, gender, immunization record, and clinical signs were obtained. Laboratory examinations were performed, which included virus isolation in tissue culture, a nucleic acid test based on virus-specific real-time polymerase chain reaction and humoral responses to the measles virus measuring immunoglobulin (Ig) M, IgG, avidity of IgG, and neutralizing antibody concentration. The measles outbreak comprised 10 laboratory confirmed cases, including three secondary and six tertiary patients. Among them, three secondary patients were unvaccinated. The index case had received two MCV doses, and the six tertiary patients were vaccinated. Both the index and tertiary patients had high specific IgG concentration with high avidity. In particular, the index patient had a markedly high neutralization antibody concentration of 425,590 mIU/mL, which indicated immunological SVF. This study first reported about measles transmission from an individual with SVF who received two vaccination doses. To prevent measles transmission and outbreak particularly in countries where measles was almost eliminated, patients with SVF for measles should be cautiously monitored.
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http://dx.doi.org/10.1016/j.vaccine.2019.11.075DOI Listing
February 2020

Transmission dynamics of HIV-1 subtype B strains in Indonesia.

Sci Rep 2019 Sep 27;9(1):13986. Epub 2019 Sep 27.

Department of Public Health, Kobe University Graduate School of Health Sciences, Hyogo, Japan.

Human immunodeficiency virus type 1 (HIV-1) and acquired immunodeficiency syndrome (AIDS) represent a major public health concern in Indonesia. Although circulating recombinant form (CRF) 01_AE is a predominant subtype in Indonesia, HIV-1 subtype B (HIV-1B) is also widely prevalent. However, the viral genetic evolution, spatial origins, and patterns of transmission of HIV-1B in Indonesia remain unclear. In the present study, we described the evolutionary characteristics and spatial-temporal transmission networks of HIV-1B in Indonesia. To elucidate the epidemiological link between HIV-1B epidemics in Indonesia and those in the remainder of the world, we conducted phylogenetic analyses of HIV-1B strains in Indonesia. Based on the results obtained, at least three epidemic clades [the Indonesia, United States (US), and China clades] of HIV-1B were found to be prevalent in Indonesia. In order to identify the potential source and transmission route of Indonesian HIV-1B strains, we performed Bayesian analyses and constructed Maximum clade credibility trees of each clade. Although some HIV-1B strains in Indonesia were introduced from Thailand, the prevalent HIV-1B strains appeared to have been directly introduced from Europe or America. Indonesian HIV-1B may have spread via the main dispersal of pandemic HIV-1B strains via the US from the Caribbean region rather than being directly introduced from Africa.
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http://dx.doi.org/10.1038/s41598-019-50491-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764962PMC
September 2019

High prevalence of equine-like G3P[8] rotavirus in children and adults with acute gastroenteritis in Thailand.

J Med Virol 2020 02 19;92(2):174-186. Epub 2019 Sep 19.

Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.

Group A rotavirus (RVA) is a major cause of acute gastroenteritis in infants and young children worldwide. This study aims to clarify the distribution of G/P types and genetic characteristics of RVAs circulating in Thailand. Between January 2014 and September 2016, 1867 stool specimens were collected from children and adults with acute gastroenteritis in six provinces in Thailand. RVAs were detected in 514/1867 (27.5%) stool specimens. G1P[8] (44.7%) was the most predominant genotype, followed by G3P[8] (33.7%), G2P[4] (11.5%), G8P[8] (7.0%), and G9P[8] (1.3%). Unusual G3P[9] (0.8%), G3P[10] (0.4%), G4P[6] (0.4%), and G10P[14] (0.2%) were also detected at low frequencies. The predominant genotype, G1P[8] (64.4%), in 2014 decreased to 6.1% in 2016. In contrast, the frequency of G3P[8] markedly increased from 5.5% in 2014 to 65.3% in 2015 and 89.8% in 2016. On polyacrylamide gel electrophoresis, most (135/140; 96.4%) of the G3P[8] strains exhibited a short RNA profile. Successful determination of the nucleotide sequences of the VP7 genes of 98 G3P[8] strains with a short RNA profile showed that they are all equine-like G3P[8] strains. On phylogenetic analysis of genome segments of two representative Thai equine-like G3P[8] strains, it was noteworthy that they possessed distinct NSP4 genes, one bovine-like and the other human-like. Thus, we found that characteristic equine-like G3P[8] strains with a short RNA electropherotype are becoming highly prevalent in children and adults in Thailand.
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http://dx.doi.org/10.1002/jmv.25591DOI Listing
February 2020

Bejel, a Nonvenereal Treponematosis, among Men Who Have Sex with Men, Japan.

Emerg Infect Dis 2019 08;25(8):1581-1583

Bejel, an endemic treponematosis caused by infection with Treponema pallidum subspecies endemicum, has not been reported in eastern Asia and the Pacific region. We report local spread of bejel among men who have sex with men in Japan. Spread was complicated by venereal syphilis.
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http://dx.doi.org/10.3201/eid2508.181690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6649352PMC
August 2019

External Quality Assessment Scheme for HIV-1 Drug-Resistance Genotyping in Thailand.

AIDS Res Hum Retroviruses 2018 12 10;34(12):1028-1035. Epub 2018 Nov 10.

3 Thailand-Japan Research Collaboration Center on Emerging and Re-emerging Infections (RCC-ERI), Nonthaburi, Thailand.

The efficacy of antiretroviral (ARV) therapy can be compromised by the emergence and transmission of HIV-1 drug-resistant strains. HIV-1 drug-resistance (DR) genotypic testing thus plays an important role in the selection of optimal treatment regimens for HIV-infected individuals. Given the complexities of the testing procedures and the variety of approaches used, there is considerable potential for results to vary between laboratories. In Thailand, the national External Quality Assessment (EQA) scheme assesses the DR genotype testing performance of laboratories. Here, we evaluated the performance of laboratories in nucleotide sequencing and compared drug-resistance-associated mutations (DRMs) in the HIV-1 protease (PR) and reverse transcriptase (RT) genes during 2010-2015. The EQA samples in the 12 panels showed predominance for the CRF01_AE (85%) and subtype B (15%). Fourteen laboratory datasets were generated: eight using TruGene (TG), two using ViroSeq (VS), and four using in-house (IH) assays. All IH and VS laboratories had penalty scores <7, whereas five of the eight TG laboratories had fluctuating penalty scores. Moreover, seven and six TG laboratories could not amplify the two identical samples, 10B and 10E samples, or the CRF01_AE. Our findings demonstrate the requirement for laboratory participation in the ongoing EQA program and the optimization of kit assays using CRF01_AE samples. Our results also indicate that one advantage of participation is that the laboratories can monitor and investigate the source of laboratory errors.
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http://dx.doi.org/10.1089/AID.2017.0299DOI Listing
December 2018

Rubella Virus Genotype 1E in Travelers Returning to Japan from Indonesia, 2017.

Emerg Infect Dis 2018 09;24(9):1763-1765

Although rubella is epidemic in Indonesia, the phylogenetic profile of circulating rubella virus strains has not been clarified. In 2017, rubella virus was detected in 2 travelers who returned from Indonesia to Japan. These strains were classified into genotype 1E lineage 2, which may be an indigenous strain in Indonesia.
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http://dx.doi.org/10.3201/eid2409.180621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106410PMC
September 2018

Characterization of a G10P[14] rotavirus strain from a diarrheic child in Thailand: Evidence for bovine-to-human zoonotic transmission.

Infect Genet Evol 2018 09 15;63:43-57. Epub 2018 May 15.

Department of Virology and Parasitology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.

An unusual rotavirus strain, DB2015-066 with the G10P[14] genotype (RVA/Human-wt/THA/DB2015-066/2015/G10P[14]), was detected in a stool sample from a child hospitalized with acute gastroenteritis in Thailand. Here, we sequenced and characterized the full-genome of the strain DB2015-066. On whole genomic analysis, strain DB2015-066 was shown to have a unique genotype constellation: G10-P[14]-I2-R2-C2-M2-A3-N2-T6-E2-H3. The backbone genes of this strain (I2-R2-C2-M2-A3-N2-T6-E2-H3) are commonly found in rotavirus strains from artiodactyls such as cattle. Furthermore, phylogenetic analysis indicated that each of the 11 genes of strain DB2015-066 could be of artiodactyl (likely bovine) origin. Thus, strain DB2015-066 appeared to be derived from through zoonotic transmission of a bovine rotavirus strain. Of note, the VP7 gene of strain DB2015-066 was located in G10 lineage-6 together with ones of bovine and bovine-like rotavirus strains, away from the clusters comprising other G10P[14] strains in G10 lineage-2/4/5/9, suggesting the occurrence of independent bovine-to-human interspecies transmission events. Our observations provide important insights into the origins of rare G10P[14] strains, and into dynamic interactions between artiodactyl and human rotavirus strains.
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http://dx.doi.org/10.1016/j.meegid.2018.05.009DOI Listing
September 2018

Foodborne Outbreak of Group G Streptococcal Pharyngitis in a School Dormitory in Osaka, Japan.

J Clin Microbiol 2018 05 25;56(5). Epub 2018 Apr 25.

Osaka Institute of Public Health, Osaka, Japan.

In September 2016, 140 patients with primary symptoms of sore throat and fever were identified in a school dormitory in Osaka, Japan. Epidemiological and laboratory investigations determined that these symptomatic conditions were from a foodborne outbreak of group G streptococcus (GGS), with GGS being isolated from samples from patients, cooks, and foods. The strain of GGS was identified as subsp. of two types ( and ). The causative food, a broccoli salad, was contaminated with the two types of subsp. , totaling 1.3 × 10 CFU/g. Pulsed-field gel electrophoresis (PFGE) of samples from patients, cooks, and foods produced similar band patterns among samples with the same type. This result suggested the possibility of exposure from the contaminated food. The average onset time was 44.9 h and the prevalence rate was 62%. This is the first report to identify the causative food of a foodborne outbreak by subsp. .
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http://dx.doi.org/10.1128/JCM.01884-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5925722PMC
May 2018

The dynamics of norovirus genotypes and genetic analysis of a novel recombinant GII.P12-GII.3 among infants and children in Bangkok, Thailand between 2014 and 2016.

Infect Genet Evol 2018 06 20;60:133-139. Epub 2018 Feb 20.

Thailand-Japan Research Collaboration Center on Emerging and Re-emerging Infections (RCC-ERI), Nonthaburi 11000, Thailand; Research Institute of Microbial Diseases, Osaka University, Suita, Osaka 565-0781, Japan; Osaka Institute of Public Health, Osaka 537-0025, Japan. Electronic address:

Norovirus (NoV) is the leading cause of viral acute gastroenteritis among all age groups in the world. We performed a molecular epidemiological study of the NoVs prevalent in Bangkok between November 2014 and July 2016 to investigate the emergence of new NoV variants in Thailand. A total of 332 stool specimens were collected from hospitalized pediatric patients with acute gastroenteritis in Bangkok, Thailand. NoVs were detected by real-time PCR. The genome of the N-terminal/shell domain was amplified, the nucleotide sequence was determined, and phylogenetic analyses were performed. GII NoV was detected in 58 (17.5%) of the 332 specimens. GII.17, a genotype strain prevalent from 2014 to mid-2015, was hardly detected and replaced by the GII.3 genotype strain. Entire genome sequencing followed by phylogenetic analysis of the GII.3 genotype strains indicated that they are new recombinant viruses, because the genome encoding ORF1 is derived from a GII.12 genotype strain, whereas that encoding ORF2-3 is from a GII.3 genotype strain. The putative recombination breakpoints with the highest statistical significance were located around the border of 3D and ORF2. The change in the prevalent strain of NoV seems to be linked to the emergence of new forms of recombinant viruses. These findings suggested that the swapping of the structural and non-structural proteins of NoV is a common mechanism by which new epidemic variants are generated in nature.
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http://dx.doi.org/10.1016/j.meegid.2018.02.028DOI Listing
June 2018

Naturally Occurring Mutations in HIV-1 CRF01_AE Capsid Affect Viral Sensitivity to Restriction Factors.

AIDS Res Hum Retroviruses 2018 04 13;34(4):382-392. Epub 2018 Feb 13.

3 National Institute of Health , Department of Medical Science, Ministry of Public Health, Nonthaburi, Thailand .

TRIM5α and MxB are known as restriction factors that inhibit the early step of intracellular HIV-1 replication cycle. Both factors are believed to interact with the incoming virus core to suppress HIV-1 infection. The extreme diversity of HIV-1 is thought to be a consequence of its propensity to mutate to escape immune responses and host restriction factors. We recently determined the capsid sequences for 144 HIV-1 CRF01_AE viruses obtained in Thailand from 2005 to 2011. In this study, we further analyzed the amino acid variations among the capsid sequences of 204 HIV-1 CRF01_AE obtained in Thailand and China, including 84 of the aforementioned 144 viruses, to detect mutations permitting escape from restriction by host factors. We found a characteristic combination of E79D, V83T, and H87Q in sequences from Chinese viruses and subsequently showed that this combination conferred partial resistance to MxB. Interestingly, this combination conferred resistance to human TRIM5α as well. The H87Q mutation alone conferred resistance to MxB in the CRF01_AE background, but not in subtype B virus. In contrast, the H87Q mutation alone conferred resistance to human TRIM5α in both the CFR01_AE and subtype B backgrounds. BLAST analysis revealed the presence of the E79D, V83T, and H87Q combination in CRF01_AE viruses isolated not only in China but also in many other countries. Although the mechanistic details as well as precise role of MxB antiviral activity in infected individuals remain to be clarified, our data suggest an interaction between MxB and the HIV-1 capsid in vivo.
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http://dx.doi.org/10.1089/AID.2017.0212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899301PMC
April 2018

Evolutionary Constraints on the Norovirus Pandemic Variant GII.4_2006b over the Five-Year Persistence in Japan.

Front Microbiol 2017 13;8:410. Epub 2017 Mar 13.

Pathogen Genomics Center, National Institute of Infectious DiseasesTokyo, Japan; Research Institute for Microbial Diseases, Osaka UniversityOsaka, Japan; Thailand-Japan Research Collaboration Center on Emerging and Re-emerging InfectionsNonthaburi, Thailand.

Norovirus GII.4 is a major cause of global outbreaks of viral gastroenteritis in humans, and has evolved by antigenic changes under the constantly changing human herd immunity. Major shift in the pandemic GII.4 strain periodically occurs concomitant with changes in the antigenic capsid protein VP1. However, how the newly emerged strain evolves after the onset of pandemic remains unclear. To address this issue, we examined molecular evolution of a pandemic lineage, termed the GII.4_2006b, by using the full-length viral genome and VP1 sequences ( = 317) from stools collected at 20 sites in Japan between 2006 and 2011. Phylogenetic tree showed a radial diversification of the genome sequences of GII.4_2006b, suggesting a rapid genetic diversification of the GII.4_2006b population from a few ancestral variants. Impressively, amino acid sequences of the variable VP1 in given seasons remained as homogeneous as those of viral enzymes under annual increase in the nucleotide diversity in the VP1 coding region. The Hamming distances between the earliest and subsequent variants indicate strong constraints on amino acid changes even for the highly variable P2 subdomain. These results show the presence of evolutionary constraints on the VP1 protein and viral enzymes, and suggest that these proteins gain near maximal levels of fitness benefits in humans around the onset of the outbreaks. These findings have implications for our understanding of molecular evolution, mechanisms of the periodic shifts in the pandemic NoV GII.4 strains, and control of the NoV GII.4 pandemic strain.
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http://dx.doi.org/10.3389/fmicb.2017.00410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346551PMC
March 2017

Comparison of genetic characteristics in the evolution of Norovirus GII.4 and GII.17.

J Med Virol 2017 08 14;89(8):1480-1484. Epub 2017 Mar 14.

Department of Microbiology, Tokyo Metropolitan Institute of Public Health, Tokyo, Japan.

The genetic characteristics of Norovirus GII.17 were evaluated. Phylogenetic analysis and comparisons of amino acid (Aa) substitutions and nonsynonymous (NS) substitutions/site/year were performed. The complete VP1 sequence of Tokyo/27-3/1976 clustered independently with GII.P17_GII.17 strains. Aa substitutions were mainly accumulated in the P2 domain. NS substitutions/site/year for Tokyo/27-3/1976 compared to Kawasaki323/2014 and Kawasaki308/2015 were 0.57 × 10 and 0.78 × 10 , respectively; for GII.4 Sydney/NSW0514/2012 compared to CHDC2094/1974 and CHDC5191/1974 were 0.93 × 10 and 1.06 × 10 , respectively. These findings imply that evolutionary diversity in the VP1 of GII.17 might be strictly constrained in contrast to that of GII.4.
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http://dx.doi.org/10.1002/jmv.24791DOI Listing
August 2017

Genomic analysis of the evolutionary lineage of Norovirus GII.4 from archival specimens during 1975-1987 in Tokyo.

J Med Virol 2017 02 13;89(2):363-367. Epub 2016 Jul 13.

Department of Microbiology, Tokyo Metropolitan Institute of Public Health, Tokyo, Japan.

This study aimed to analyze NoV GII.4 sequences from archival specimens obtained during 1975-1987 by comparing them with reference sequences. The first NoV GII.P4_GII.4 sequence was identified in 1980. NoV GII.4 collected in 1970 had a GII.P1_GII.4 sequence. These results indicate that the GII.P4_GII.4 sequence may be the result of a recombination that might have occurred around 1980. Amino acid substitutions based on this replacement were mainly accumulated in the NTPase, p22, and RdRp regions. The emergence of GII.P4_GII.4 sequence is considered to have ended the major prevalence of NoV GII.4. J. Med. Virol. 89:363-367, 2017. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jmv.24624DOI Listing
February 2017

Norovirus epidemics caused by new GII.2 chimera viruses in 2012-2014 in Japan.

Infect Genet Evol 2016 08 22;42:49-52. Epub 2016 Apr 22.

Osaka University, Osaka 565-0871, Japan.

The new GII.2 variant collected from May 2012-March 2014 consisted of GII.15 and GII.2 genomes, in which the putative recombination points found in the boundary region between ORF1 and ORF2. These findings suggested that the swapping of structural and non-structural proteins is a common mechanism for generating new epidemic variants in nature.
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http://dx.doi.org/10.1016/j.meegid.2016.04.026DOI Listing
August 2016

Circulation of HIV-1 Multiple Complexity Recombinant Forms Among Female Sex Workers Recently Infected with HIV-1 in Thailand.

AIDS Res Hum Retroviruses 2016 07 19;32(7):694-701. Epub 2016 Apr 19.

4 Research Institute of Microbial Diseases, Osaka University , Osaka, Japan .

The circulating subtype distribution of HIV-1 has not been well characterized in female sex worker (FSW) populations in Thailand. To understand the mechanisms and interrelationships of epidemics involving FSWs in Thailand, we performed a large molecular epidemiological study of FSWs aged 25 years with recently acquired HIV-1 infections. The samples were collected in 2005, 2007, 2009, and 2011 in 38 provinces, representing every region of Thailand. After gag (p24), pol (pro-RT), and env (C2/V3) were sequenced, comprehensive genome analysis was performed. Genetic subtypes were determined in 159 plasma samples. The percentage of circulating recombinant forms (CRFs) CRF01_AE (90.6%) predominated, while subtype B (1.3%), other CRFs (1.9%), and unique recombinant forms (URFs) (6.2%) were identified as minor populations. Interestingly, the unique recombinant nature of these HIV-1 strains was verified in 10 specimens, indicating the presence of new forms of HIV-1 intersubtypes G/A, C/B, AE/B/C, and AE/B with different recombination breakpoints. Subtype B has contributed to these new generations of unique CRF01/B recombinants, especially in the pol (RT) gene, in which the template switching of the RT genomes occurred during reverse transcription. These results imply that the several unique recombinant viruses circulating in Thailand were probably generated in the population or introduced from neighboring countries. Our study helps clarify the patterns of viral transmission and define transmission pathways in Thailand.
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http://dx.doi.org/10.1089/AID.2015.0371DOI Listing
July 2016

Transmission and Demographic Dynamics of Coxsackievirus B1.

PLoS One 2015 8;10(6):e0129272. Epub 2015 Jun 8.

Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan; Thailand-Japan Research Collaboration Center on Emerging and Re-emerging Infections, Research Institute of Microbial Diseases, Osaka University, Nonthaburi, Thailand.

The infectious activity of coxsackievirus B1 (CV-B1) in Taiwan was high from 2008 to 2010, following an alarming increase in severe neonate disease in the United States (US). To examine the relationship between CV-B1 strains isolated in Taiwan and those from other parts of the world, we performed a phylodynamic study using VP1 and partial 3Dpol (414 nt) sequences from 22 strains of CV-B1 isolated in Taiwan (1989-2010) and compared them to sequences from strains isolated worldwide. Phylogenetic trees were constructed by neighbor-joining, maximum likelihood, and Bayesian Monte Carlo Markov Chain methods. Four genotypes (GI-IV) in the VP1 region of CV-B1 and three genotypes (GA-C) in the 3Dpol region of enterovirus B were identified and had high support values. The phylogenetic analysis indicates that the GI and GIII strains in VP1 were geographically distributed in Taiwan (1993-1994) and in India (2007-2009). On the other hand, the GII and GIV strains appear to have a wider spatiotemporal distribution and ladder-like topology A stair-like phylogeny was observed in the VP1 region indicating that the phylogeny of the virus may be affected by different selection pressures in the specified regions. Further, most of the GI and GII strains in the VP1 tree were clustered together in GA in the 3D tree, while the GIV strains diverged into GB and GC. Taken together, these data provide important insights into the population dynamics of CV-B1 and indicate that incongruencies in specific gene regions may contribute to spatiotemporal patterns of epidemicity for this virus.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0129272PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4460132PMC
March 2016

Long-term viral shedding and viral genome mutation in norovirus infection.

J Med Virol 2015 Nov 19;87(11):1872-80. Epub 2015 May 19.

Sakai City Institute of Public Health, Sakai, Osaka, Japan.

The duration of viral shedding in the patients from two outbreaks and four sporadic cases of norovirus (NoV) infections was investigated. The longest period of viral shedding into feces was for 173 days in an inpatient from one case of outbreak. The VP1 sequence from two long-term viral shedding cases in the outbreak revealed four synonymous and one non-synonymous mutations in one inpatient at 26 days from the onset of illness, and nine synonymous and two non-synonymous mutations and a deletion, 10 synonymous mutations and a deletion in other inpatient at 29 days and 54 days from the onset of illness, respectively. Ten of the 11 amino acid positions detected in these two inpatients were in the outermost P2 domain of the viral capsid protein, and mutations at positions 295, 297, and 394 were shared in the inpatients. Mutations in the P2 domain were in epitopes A and D or near epitopes A, C, and E, suggesting that the long-term carrier state of norovirus infection contributes to the generation of escape mutants by host immunoselection.
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http://dx.doi.org/10.1002/jmv.24242DOI Listing
November 2015

Dominant mutations in ORAI1 cause tubular aggregate myopathy with hypocalcemia via constitutive activation of store-operated Ca²⁺ channels.

Hum Mol Genet 2015 Feb 16;24(3):637-48. Epub 2014 Sep 16.

Department of Clinical Development, Translational Medical Center, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8556, Japan Department of Neuromuscular Research and.

The store-operated Ca(2+) release-activated Ca(2+) (CRAC) channel is activated by diminished luminal Ca(2+) levels in the endoplasmic reticulum and sarcoplasmic reticulum (SR), and constitutes one of the major Ca(2+) entry pathways in various tissues. Tubular aggregates (TAs) are abnormal structures in the skeletal muscle, and although their mechanism of formation has not been clarified, altered Ca(2+) homeostasis related to a disordered SR is suggested to be one of the main contributing factors. TA myopathy is a hereditary muscle disorder that is pathologically characterized by the presence of TAs. Recently, dominant mutations in the STIM1 gene, encoding a Ca(2+) sensor that controls CRAC channels, have been identified to cause tubular aggregate myopathy (TAM). Here, we identified heterozygous missense mutations in the ORAI1 gene, encoding the CRAC channel itself, in three families affected by dominantly inherited TAM with hypocalcemia. Skeletal myotubes from an affected individual and HEK293 cells expressing mutated ORAI1 proteins displayed spontaneous extracellular Ca(2+) entry into cells without diminishment of luminal Ca(2+) or the association with STIM1. Our results indicate that STIM1-independent activation of CRAC channels induced by dominant mutations in ORAI1 cause altered Ca(2+) homeostasis, resulting in TAM with hypocalcemia.
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http://dx.doi.org/10.1093/hmg/ddu477DOI Listing
February 2015

[A mechanism of norovirus pandemic based on comprehensive genome analysis].

Kansenshogaku Zasshi 2012 Sep;86(5):563-8

Pathogen Genomics Center, National Institute of Infectious Diseases.

Norovirus GII.4 is a major etiological agent of acute viral gastroenteritis worldwide. We examined GII.4 evolution using 277 near-full-length GII.4 genome sequences from human stool specimens collected at 20 sites in Japan between May 2006 and March 2010. We found outbreaks of 8 monophyletic GII.4 subtypes, among which a single subtype, termed 2006b, had continually predominated (222/277: 80.7%). Four of the 8 GII.4 subtypes were chimera viruses of recently prevalent GII.4 subtypes. Notably, single putative recombination breakpoints with the highest statistical significance were constantly located around the border of open reading frame 1 (ORF) 1 and ORF 2 (P<0.0001), suggesting outgrowth of specific recombinant viruses in the outbreaks. The GII.4 subtypes had many unique amino acids at the time of their outbreaks, especially in the N-term, 3A-like, and capsid proteins. Unique amino acids in the capsid were preferentially positioned on the outer surface loops of the protruding P2 domain. These data and computer-assisted structural study of NoV capsid protein are compatible with a model of antigenic drift with tuning of the structure-functions of multiple proteins for the survival strategy of GII.4 2006b variant.
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http://dx.doi.org/10.11150/kansenshogakuzasshi.86.563DOI Listing
September 2012

[Basic knowledge of norovirus epidemic and methods of examination].

Nihon Rinsho 2012 Aug;70(8):1272-5

Pathogen Genomics Center, National Institute of Infectious Diseases.

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August 2012

The indonesian variants of CRF33_01B: Near-full length sequence analysis.

AIDS Res Hum Retroviruses 2011 Jan 19;27(1):97-102. Epub 2010 Oct 19.

Department of Microbiology, Iwate Medical University, Morioka, Japan.

Cocirculation of subtype B and CRF01_AE in Southeast Asia has led to the establishment of new recombinant forms. In our previous study, we found five samples suspected of being recombinants between subtype B and CRF01_AE, and here, we analyzed near full-length sequences of two samples and compared them to known CRFs_01B, subtype B, and CRF01_AE. Five overlapped segments were amplified with nested PCR from PBMC DNA, sequenced, and analyzed for genome mosaicism. The two Indonesian samples, 07IDJKT189 and 07IDJKT194, showed genome-mosaic patterns similar to CRF33_01B references from Malaysia, with one short segment in the 3' end of the p31 integrase-coding region, which was rather more similar to subtype B than CRF01_AE, consisting of unclassified sequences. These results suggest gene-specific continuous diversification and spread of the CRF33_01B genomes in Southeast Asia.
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http://dx.doi.org/10.1089/aid.2010.0163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5586156PMC
January 2011