Publications by authors named "Chang Kweng Lim"

Article Synopsis
  • - The West Nile virus (WNV) subtype Kunjin, prevalent in Australia, has been studied, particularly the classical strain OR393, which contains two virus types: small plaque-forming (SP) and large plaque-forming (LP).
  • - Differences in amino acids at specific positions in the E protein between SP and LP influence their growth rates and the ability to form plaques, with SP growing slightly faster and being glycosylated while LP is not.
  • - The study reveals that small changes in the E protein can significantly alter the virulence of the virus, indicating that the LP variant exhibits enhanced neuroinvasive potential compared to SP and that the amino acid Phe in LP can mutate to Ser, aiding the
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Severe fever with thrombocytopenia syndrome (SFTS) virus, a tick-borne bunyavirus, causes a severe/fatal disease termed SFTS; however, the viral virulence is not fully understood. The viral non-structural protein, NSs, is the sole known virulence factor. NSs disturbs host innate immune responses and an NSs-mutant SFTS virus causes no disease in an SFTS animal model.

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Heartland virus (HRTV) causes generalized symptoms, severe shock, and multiple organ failure. We previously reported that interferon-α/β receptor knockout (IFNAR) mice infected intraperitoneally with 1 × 10 tissue culture-infective dose (TCID) of HRTV died, while those subcutaneously infected with the same dose of HRTV did not. The pathophysiology of IFNAR mice infected with HRTV and the mechanism underlying the difference in disease severity, which depends on HRTV infection route, were analyzed in this study.

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Yokose virus (YOKV) is a bat-associated no-known vector flavivirus group member. We investigated the replication ability of YOKV in mosquito-derived C6/36 cells. YOKV grew in C6/36 cells, but its kinetics of YOKV was markedly slower than those of other mosquito-borne flaviviruses.

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Dengue is a febrile illness caused by the dengue virus (DENV) that belongs to the genus Flavivirus in the family Flaviviridae. Cross-reactivity between flaviviruses poses a challenge while interpreting serological test results. In the present study, the cross-reactivity of sera of the patients with dengue, who traveled from Japan to DENV-endemic countries, was analyzed by using an enzyme-linked immunosorbent assay (ELISA) and neutralization test (NT).

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Article Synopsis
  • * The strain showed intermediate growth levels in monkey cells compared to other genotypes and had varying levels of neuroinvasiveness, but overall neurovirulence was similar across tested strains.
  • * Serological tests revealed that while neutralizing antibody responses were comparable for some strains, the response to GIV JEV was lower, indicating a need for more research to fully understand this genotype's characteristics.
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  • Japanese encephalitis virus (JEV) is a mosquito-borne virus classified in the Flavivirus family, with five different genotypes (G1-G5) based on genetic variations of its envelope protein.
  • JEV G3 was previously dominant in Japan but was replaced by G1 in the early 1990s; however, G3 re-emerged in 2004 and was found in swine and cows in Kochi Prefecture in 2018.
  • Recent genetic sequencing of JEV isolates shows variations between G3 strains from 2004 and 2018, confirming the presence of both JEV G1 and G3 in the Kochi area.
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The Chikungunya virus (CHIKV), an enveloped RNA virus that has been identified in over 40 countries and is considered a growing threat to public health worldwide. However, there is no preventive vaccine or specific therapeutic drug for CHIKV infection. To identify a new inhibitor against CHIKV infection, this study constructed a subgenomic RNA replicon expressing the secretory Gaussia luciferase (Gluc) based on the CHIKV SL11131 strain.

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The rabies virus is widely distributed and vaccines are an important strategy to prevent its spread. The whole-genome sequences of rabies strains in relation to vaccine development provide essential information to maintain vaccine quality and develop new vaccines. However, the genetic characteristics of the purified chick embryo cell culture rabies vaccine, KM Biologics (PCECV-KMB), developed in Japan in the 1970s, have not been explored.

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Heartland bandavirus (HRTV) is an emerging tick-borne virus that is distributed in the United States and that causes febrile illness with thrombocytopenia and leukocytopenia. It is genetically close to Dabie bandavirus, which is well known as severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV). The mortality rate of human HRTV infection is approximately 10%; however, neither approved anti-HRTV agents nor vaccines exist.

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  • Heartland bandavirus (HRTV) is a tick-borne virus discovered in Missouri in 2009, causing symptoms like fever, fatigue, and muscle pain in humans.
  • A reverse genetics system for HRTV was developed, yielding a nonstructural protein (NSs)-knockout variant (rHRTV-NSsKO), which interferes with the body’s innate immune response.
  • The rHRTV-NSsKO was found to be less harmful in mouse models and shows potential as a vaccine candidate, indicating that NSs plays a key role in HRTV virulence.
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Owing to genotype-specific neutralizing antibodies, analyzing differences in the immunogenic variation among dengue virus (DENV) genotypes is central to effective vaccine development. Herein, we characterized the viral kinetics and antibody response induced by DENV type 2 Asian I (AI) and Asian/American (AA) genotypes using marmosets () as models. Two groups of marmosets were inoculated with AI and AA genotypes, and serial plasma samples were collected.

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Genotype V (GV) Japanese encephalitis virus (JEV) has emerged in Korea and China since 2009. Recent findings suggest that current Japanese encephalitis (JE) vaccines may reduce the ability to induce neutralizing antibodies against GV JEV compared to other genotypes. This study sought to produce a novel live attenuated JE vaccine with a high efficacy against GV JEV.

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Various pathogens, such as Ebola virus, Marburg virus, Nipah virus, Hendra virus, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and SARS-CoV-2, are threatening human health worldwide. The natural hosts of these pathogens are thought to be bats. The rousette bat, a megabat, is thought to be a natural reservoir of filoviruses, including Ebola and Marburg viruses.

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Zika virus (ZIKV) is a mosquito-borne flavivirus that causes febrile illness. The recent spread of ZIKV from Asia to the Americas via the Pacific region has revealed unprecedented features of ZIKV, including transplacental congenital infection causing microcephaly. Amino acid changes have been hypothesized to underlie the spread and novel features of American ZIKV strains; however, the relationship between genetic changes and the epidemic remains controversial.

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Zika virus (ZIKV) infection during pregnancy causes a wide spectrum of congenital abnormalities and postnatal developmental sequelae such as fetal loss, intrauterine growth restriction (IUGR), microcephaly, or motor and neurodevelopmental disorders. Here, we investigated whether a mouse pregnancy model recapitulated a wide range of symptoms after congenital ZIKV infection, and whether the embryonic age of congenital infection changed the fetal or postnatal outcomes. Infection with ZIKV strain PRVABC59 from embryonic day 6.

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Zika virus (ZIKV) strains are classified into the African and Asian genotypes. The higher virulence of the African MR766 strain, which has been used extensively in ZIKV research, in adult IFNα/β receptor knockout (IFNAR-/-) mice is widely viewed as an artifact associated with mouse adaptation due to at least 146 passages in wild-type suckling mouse brains. To gain insights into the molecular determinants of MR766's virulence, a series of genes from MR766 were swapped with those from the Asian genotype PRVABC59 isolate, which is less virulent in IFNAR-/- mice.

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Introduction: Several clinical studies have reported the efficacy of favipiravir in reducing viral load and shortening the duration of symptoms. However, the viability of SARS-CoV-2 in the context of favipiravir therapy and the potential for resistance development is unclear.

Methods: We sequenced SARS-CoV-2 in nasopharyngeal specimens collected from patients who participated in a randomized clinical trial of favipiravir at hospitals across Japan between March and May 2020.

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Chikungunya virus (CHIKV) is a mosquito-borne RNA virus that causes Chikungunya fever in humans. In this study, we generated two DNA-based CHIKV infectious clones derived from an Indian Ocean Lineage SL11131 strain and a prototype Ross strain. When the replication capabilities of the infectious CHIKV in various cell lines were evaluated, the SL11131 strain was found to replicate more efficiently than the Ross strain in Aedes albopictus C6/36 cells, whereas SL11131 underwent limited replication in a BHK-21-derivative cell line named BHK-DRV.

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Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

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Lymphocytic choriomeningitis virus (LCMV) is a prototypic arenavirus. The function of untranslated regions (UTRs) of the LCMV genome has not been well studied except for the extreme 19 nucleotide residues of both the 5' and 3' termini. There are internal UTRs composed of 58 and 41 nucleotide residues in the 5' and 3' UTRs, respectively, in the LCMV S segment.

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Dengue fever outbreaks have been repeatedly reported in Côte d'Ivoire. During the 2019 outbreak, DENV-1 was the predominant strain and phylogenetic analysis of the DENV-1 genome obtained from the present patient who returned to Japan in January 2019 revealed a high homology with the 2013-2014 Southeast Asian strains. In a previous outbreak in 2017, DENV-1 accounted for 5% of the DENV serotypes.

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We previously showed that the growth ability of the Japanese encephalitis virus (JEV) genotype V (GV) strain Muar is clearly lower than that of the genotype I (GI) JEV strain Mie/41/2002 in murine neuroblastoma cells. Here, we sought to identify the region in GV JEV that is involved in its low growth potential in cultured cells. An intertypic virus containing the NS1-3 region of Muar in the Mie/41/2002 backbone (NS1-3) exhibited a markedly diminished growth ability in murine neuroblastoma cells.

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We previously showed that the Japanese encephalitis virus (JEV) genotype V (GV) strain Muar exhibits significantly higher virulence in mice than the genotype I (GI) JEV strain Mie/41/2002. In this study, we attempted to identify the region responsible for the increased virulence of GV JEV using recombinant intertypic and single mutant JEVs. Intertypic viruses containing the GV E region in the Mie/41/2002 backbone showed increased pathogenicity in mice.

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