[show abstract][hide abstract] ABSTRACT: The continuing threat of dengue fever necessitates a comprehensive characterisation of its epidemiological trends. Phylogenetic and recombination events were reconstructed based on 100 worldwide dengue virus (DENV) type 1 genome sequences with an outgroup (prototypes of DENV2-4). The phylodynamic characteristics and site-specific variation were then analysed using data without the outgroup. Five genotypes (GI-GV) and a ladder-like structure with short terminal branch topology were observed in this study. Apparently, the transmission of DENV1 was geographically random before gradual localising with human activity as GI-GIII in South Asia, GIV in the South Pacific, and GV in the Americas. Genotypes IV and V have recently shown higher population densities compared to older genotypes. All codon regions and all tree branches were skewed toward a negative selection, which indicated that their variation was restricted by protein function. Notably, multi-epistatic interaction sites were found in both PrM 221 and NS3 1730. Recombination events accumulated in regions E, NS3-NS4A, and particularly in region NS5. The estimated coevolution pattern also highlights the need for further study of the biological role of protein PrM 221 and NS3 1730. The recent transmission of emergent GV sublineages into Central America and Europe mandates closely monitoring of genotype interaction and succession.
PLoS ONE 01/2013; 8(9):e74165. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate the molecular epidemiology of Taiwanese Echovirus 30 (E-30) strains, we analyzed the 876 bp sequence of the VP1 gene from 32 Taiwanese strains isolated in 1988-2008, 498 reference sequences, and one Echovirus 21 strain as the out-group. Phylogenetic analysis detected six E-30 genotypes (designated GI-GVI) that had circulated globally during the past five decades. The genotypes varied widely in geographic distribution and circulation half-life. The GI, GII, and GV were ancient genotypes in which the first strains emerged in the 1950s. The GIII was a reemerging genotype, in which strains had first appeared in Colombia in 1995 before reemerging in the New Independent States (NIS) in 2003. The GIV, an emerging genotype that recently appeared in Asia in 2003, was closely related to the ancient genotypes. The GVI was the circulating genotype, which included eight clusters (A-H) that had circulated since 1967. No GVI-A, C, D, or E strains have been identified during the past 10 years. The GVI-B first appeared in China in 1984 and later in Russia and Asia in the 2000s. The GVI-F, G, and H strains, which comprised the prevalent clusters, had been dominant in Asia Pacific area, globally, and Europe, respectively. Taiwanese strains were classified into GVI-D (1988-1989), GVI-F (1993-2004), and GVI-G (1993-2008). The quiescence period of E-30 is longer in Taiwan (5-8 years) than in other countries (3-5 years).
[show abstract][hide abstract] ABSTRACT: Molecular epidemiological characteristics are needed to understand the impact of Coxsackievirus B3 (CV-B3) infection, since no CV-B3 genotyping literature is available. Twenty-nine CV-B3 Taiwan strains obtained from 1992 to 2005 were analyzed. A phylogenetic tree was constructed based on the 290 nucleotide sequence of the VP1 gene of Taiwan isolates and in 91 other CV-B3 GenBank sequences. Five genotypes (GI-GV) were depicted. The GI, GII, and GIII were dominant in America and Europe, whereas GIV and GV were prevalent in Asia. In Taiwan, a transient outbreak of GIV occurred in 2000, while GV has been the main genotype circulating since 1992. Patient age ranged from 0.1 to 81 months (median, 4.3 months). The male:female ratio was 1.9:1. More than 60% (17/29) of cases involved children younger than 1 year. Half of them contracted respiratory tract infection (12/24). Nine of the 24 (37.5%) cases with available medical records had central nervous system (CNS) involvement. Eight of the nine patients were younger than 3 months. The CV-B3 has evolved and circulated for the past 60 years. Although the nucleotide sequence of the VP1 is highly variably, amino acids were relatively conserved within the same genotype of CV-B3. CNS infections were not associated with a specific strain or genotype. The CV-B3 poses a significant health threat to children younger than 1 year, especially those younger than 3 months old.
Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 08/2010; 10(6):777-84. · 3.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: Genome type analysis of adenovirus type 3 (Ad3) in Taiwan identified four types (Ad3a, Ad3a2, Ad3a1, Ad3-7) during 1983-2005. Ad3a was the major type during 1983-1999, while Ad3a2 was the predominant type from 2001 to 2005. Phylogenetic analysis of the hexon gene of 23 isolates revealed that most Ad3a2 and Ad3-7 isolates belonged to one cluster, and most Ad3a isolates to the other cluster. The clinical manifestations included respiratory tract infections, acute gastroenteritis, hand-foot-and-mouth disease, febrile convulsion and pharyngoconjunctival fever. In conclusion, Ad3a2 has replaced Ad3a as the most common genome type in Taiwan since 2001.
Archives of Virology 02/2010; 155(2):287-92. · 2.03 Impact Factor
[show abstract][hide abstract] ABSTRACT: To elucidate the epidemiological relationships between ND outbreaks and genetic lineages, a portion of the F gene (535 bp) and the full-length HN gene (1922 bp) of recent Taiwanese NDVs isolated in 2002-2008 was amplified by reverse transcription (RT)-polymerase chain reaction (PCR) and sequenced. Only a portion of above amplified PCR products of the F and HN genes (374 and 1713 bp) and their deduced amino acid residues were compared with the other 60 NDVs retrieved from GenBank. Most (29/30) of the recent Taiwanese isolates were clustered in subgenotype VIIe while only one isolate was classified as subgenotype VIIc. All the 29 isolates of subgenotype VIIe were further subclassified and termed provisionally as sub-subgenotypes VIIe2 (13 isolates), VIIe3 (5 isolates), and VIIe4 (11 isolates). The sub-subgenotype VIIe2 isolates possessing the motif (112)R-R-Q-K-R-F(117) and amino acid residue substitutions at positions 23 (L to F) and 90 (T to A) were collected during 2002-2005. The sub-subgenotype VIIe3 isolates possessing the motif (112)R-R-K-K-R-F(117) and amino acid residue substitutions at positions 74 (E to G) and 75 (A to G) within epitopes and 114 (Q to K) within cleavage site of F protein were collected during 2003-2006. The sub-subgenotype VIIe4 isolates possessing the motif (112)R-R-Q-K-R-F(117) and amino acid residue substitutions at positions 23 (L to F), 26 (I to T), and 90 (T to A) were collected during 2007-2008. All the NDV isolates in this study exhibited a high intra-cerebral pathogenicity index (ICPI), they were all classified as velogenic type of NDVs. The sub-subgenotype VIIe2 and VIIe4 viruses are now dominant and have been implicated in most of the recent ND outbreaks in Taiwan. Phylogenetic analysis of these isolates revealed that they may have evolved from previously reported local strains (VIIe1). This finding is essential for improving the disease control strategies and development of vaccines for ND.
Virus Research 11/2009; 147(2):247-57. · 2.75 Impact Factor
[show abstract][hide abstract] ABSTRACT: Epidemics of acute hemorrhagic conjunctivitis (AHC) caused by a coxsackievirus A24 variant (CA24v) appeared in Taiwan in 2000-2002 and again in 2006-2007.
To analyze the molecular epidemiology of CA24v in recent outbreaks in Taiwan.
A 510bp fragment of 3C(pro) region was analyzed in 30 CA24v isolates during 2000-2007. Phylogenetic tree was constructed along with 130 CA24v isolates available from the GenBank. Moreover, the 235bp of 3'VP1 region was similarly analyzed in 15 randomly selected strains isolated during 1985-2007. Phylogenetic dendrogram was constructed for the 3'VP1 region in 105 CA24v strains worldwide. Genetic distances were calculated using Kimura 2-parameter model, and phylogenetic trees were constructed by neighbor-joining method.
The 3C(pro) dendrogram depicted genotype IV (GIV), a new genotype that can be further divided into three clusters (C1-C3). The 2000-2002 outbreaks were caused by genotype IV-cluster 1 (GIV-C1) and GIV-C2. Strains isolated in the 2006-2007 outbreak belong to GIV-C3, also in the same cluster as Singapore strains from 2005. Analysis on 3'VP1 revealed only GI, GIII and GIV in line with the classification in 3C(pro) dendrogram. All genotype IV strains were also divided into three clusters, though the GIV-C 2' were isolated from broader geographic areas and over a longer period of time.
Analysis of the 3C(pro) region is more insightful than the 3'VP1 region in the molecular epidemiology of CA24v. The 3C(pro) dendrogram accurately and chronologically identified all stains involved in the worldwide outbreaks.
Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 06/2009; 45(4):285-91. · 3.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: Enterovirus outbreaks caused by Coxsackievirus B4 (CB4) in Taiwan in 2004 and 2008.
To retrospectively analyze the molecular epidemiology and pathogenicity of CB4 in Taiwan.
This study analyzed twenty-three CB4 strains isolated in Taiwan during 1993-2004. Sequence variations data were obtained using 420 bp of VP4/VP2 region and 331 bp of 3' VP1 region. Phylogenetic dendrograms were constructed with other CB4 sequences in Genebank. The clinical manifestations of CB4 infection were examined by retrospectively reviewing medical records of infected patients.
Three CB4 genotypes were identified: genotypes II, IVb and VIII. Genotype VIII, a new and geographically distinct cluster, has been isolated in South Korea, China and Taiwan. This genotype was isolated in twelve of twenty-three CB4 patients treated in Taiwan during 1997-2004. Eight of twenty-three strains belonging to genotype II, now the major genotype worldwide, were first identified in Taiwan in 2000. Three isolates (identified 1993-1994) analyzed in this study belonged to genotype IVb. In this retrospective follow-up study of sixteen patients with CB4 infection, the median patient age at the time of infection diagnosis was 4-year-old (range, 18 days to 10-year-old), and male-female ratio was 1:1. None of the sixteen patients suffered IDDM or myocarditis after their B4 infection episodes; four had Attention Deficit Hyperactivity Disorder (ADHD) and/or tic disorders (TDs) at follow-up.
Genotypes II and VIII of CB4 have co-circulated in Taiwan since 2000. Controlled studies are needed to evaluate a possible association between ADHD and TDs with CB4 infection.
Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 05/2009; 45(1):16-22. · 3.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: The genetic relationships among dengue virus serotype 2 (DEN-2) isolates from the Taiwan 2002 epidemic were studied by sequence analysis of the envelope (E) and nonstructural protein 1 (NS1) genes. A 0-0.4% divergence among 10 isolates revealed an epidemic strain in the outbreak. Phylogenetic study demonstrated that the 2002 Taiwan isolates were of the Cosmopolitan genotype, which is different from the Asian 1 and Asian 2 genotypes of Taiwan DEN-2 isolates from 1981 to 1998 and the American/Asian genotype of 2005 Taiwan isolates. Although grouping results from both E and NS1 gene sequence analyses were the same, the usage of the NS1 gene as a sequence analysis target has not been validated for the lower bootstrap support values of branches in the phylogenetic tree. Our result showing the same genotype changes in Taiwan and Philippines isolates suggests strain transfer of DEN-2 to nearby countries resulting in the same trend of genotype change.
The Kaohsiung journal of medical sciences 09/2008; 24(8):398-407. · 0.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: Dengue virus serotype 3 (dengue-3) has been classified into five genotypes (I-V) by phylogenetic analysis based on different viral genes. To investigate the genetic variability and evolutionary character of the dengue-3 isolates in southern Taiwan from 2005 to 2006, we analyzed the 290 nucleotides of the core (C) gene of 12 dengue-3 isolates and compared them with the published C gene sequences of global dengue-3 strains available in GenBank, including four isolates from 1998 and one isolate from 1999, from Taiwan. The dengue-3 viruses from 2005 to 2006 were not from continuous spread of an epidemic strain or re-emergence of the 2005 strains in the 2-year period because there was a 5.4-6.2% difference in the 290 nucleotides of the C gene and different genotypes between the 2005 and 2006 strains. Most of the nucleotide changes, compared with a prototype dengue-3 virus, H87, occurred in the third codon position and were non-synonymous mutations occurring naturally in the C gene. In addition, there was no consistent difference in the 290 nucleotides of the C gene between eight dengue fever and two dengue hemorrhagic fever isolates from 2006. The phylogenetic analysis indicates that the isolates from the 1998, 1999 and 2006 Taiwan dengue-3 epidemics are phylogenetically related and belong to genotype III. It was noted that the 2005 Taiwan dengue-3 isolates belong to another genotype. This molecular epidemiology study of dengue-3 viruses in Taiwan helps to elucidate whether there is a continuation of outbreaks in consecutive years, re-emergence of endemic dengue virus, or introduction of strains from other countries.
The Kaohsiung journal of medical sciences 03/2008; 24(2):55-62. · 0.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: In Taiwan, enterovirus 71 (EV71) has played an important role in severe enterovirus-related cases every year since the devastating outbreak in 1998. Three genogroups A, B, C occur worldwide; with the B and C genogroups being subdivided into B1-B4 and C1-C4 subgenogroups respectively. To understand the mutation of the EV71 genogroup in Taiwan before and after 1998, a total of 54 worldwide strains were studied including 41 Taiwanese strains obtained in 1986 and 1998-2004. A fragment of 207 bp of the VP4 region was amplified and sequenced. Genetic analysis was performed using MEGA software (version 3.0) for the nucleotide sequence alignment and phylogenetic analysis. In Taiwan, the subgenogroup B1 was predominant before 1998 while subgenogroup C2 was the major etiologic group in 1998 outbreak. A minor etiologic group outbreak in 1998, subgenogroup B4, became predominant during the period from 1999 to 2003. In this study, subgenogroup C4 emerged and became predominant in 2004 in Taiwan. The nucleotide differences between B1 and C2, C2 and B4, B4 and C4 were 20%-26%, 19%-27%, 18%-22%, respectively. Nucleotide sequence alignment revealed 67 substitutions. Most of the substitutions (62/67) were silent mutations. This is the first report about the emergence of EV71 subgenogroup C4 in Taiwan.
Journal of Medical Virology 03/2006; 78(2):254-62. · 2.37 Impact Factor
[show abstract][hide abstract] ABSTRACT: Enteroviruses are environmental triggers in the pathogenesis of type 1 diabetes mellitus (DM). A sequence of six identical amino acids (PEVKEK) is shared by the 2C protein of Coxsackie virus B and the glutamic acid decarboxylase (GAD) molecules. Between 1995 and 2002, we investigated 22 Coxsackie virus B5 (CVB5) isolates from southern Taiwan. Four of these isolates were obtained from four new-onset type 1 DM patients with diabetic ketoacidosis. We compared a 300 nucleotide sequence in the 2C protein gene (p2C) in 24 CVB5 isolates (4 diabetogenic, 18 non-diabetogenic and 2 prototype). We found 0.3-10% nucleotide differences. In the four isolates from type 1 DM patients, there was only 2.4-3.4% nucleotide difference, and there was only 1.7-7.1% nucleotide difference between type 1 DM isolates and non-diabetogenic isolates. Comparison of the nucleotide sequence between prototype virus and 22 CVB5 isolates revealed 18.4-24.1% difference. Twenty-one CVB5 isolates from type 1 DM and non-type 1 DM patients contained the PEVKEK sequence, as shown by the p2C nucleotide sequence. Our data showed that the viral p2C sequence with homology with GAD is highly conserved in CVB5 isolates. There was no difference between diabetogenic and non-diabetogenic CVB5 isolates. All four type 1 DM patients had at least one of the genetic susceptibility alleles HLA-DR, DQA1, DQB1. Other genetic and autoimmune factors such as HLA genetic susceptibility and GAD may also play important roles in the pathogenesis in type 1 DM.
The Kaohsiung journal of medical sciences 12/2004; 20(11):525-32. · 0.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: Adenoviruses account for 5-10 per cent of respiratory illnesses in children. To analyse the clinical features and the temporal frequency in acute adenoviral respiratory infections in hospitalized children in southern Taiwan, a total of 4333 children who were admitted to the Department of Pediatrics, Kaohsiung Municipal Hsiaokang (KMHK) Hospital, with clinical evidences of acute respiratory infections between January 2001 and December 2002 were studied. Adenoviruses were isolated from 317 patients with an isolation rate of 7.67 per cent. Serotype analysis was performed by polymerase chain reaction (PCR) and/or PCR-restriction fragment length polymorphism (PCR-RFLP) in 186 specimens. In 2001, adenovirus type 4 was found in the majority (57 per cent), followed by type 1.5.6 (15 per cent), type 2 (13 per cent), type 14 (8 per cent), type 3 (5 per cent), and type 7 (2 per cent). In 2002, type 3 became the major type (46 per cent), whereas the previously predominant type 4 decreased to 6 per cent, and type 7 increased from 2 to 19 per cent. The symptoms and signs included fever (98.7 percent), cough (77.6 per cent), abnormal breathing sounds (crackles and/or wheezing 23.3 per cent), abdominal pain (18.9 per cent), vomiting (21.8 per cent), and diarrhea (25.2 per cent). The mean duration of fever was 4.8 days (range 0-19 days). In the 186 cases in whom serotypes were analysed, pharyngitis and tonsillitis (47.8 per cent) were the most common presentation, followed by pneumonia (25.2 per cent), bronchitis (12.9 per cent), and pharyngoconjunctival fever (PCF) (7.6 per cent). Children between 4 and 8 years old were the most common group of patients with respiratory adenoviral infections. Our patients all had good prognosis. This adenoviruses molecular epidemiological study provides information that helps physicians in clinical differential diagnosis and treatment of respiratory adenoviral infection in children in southern Taiwan.
Journal of Tropical Pediatrics 11/2004; 50(5):279-84. · 1.01 Impact Factor
[show abstract][hide abstract] ABSTRACT: From November 1999 to December 2001, three outbreaks of adenovirus (Ad) respiratory infection occurred in southern Taiwan. To determine the circulating serotypes and molecular epidemiology, a total of 524 virus strains were randomly selected from 1,064 strains isolated from 1981 to 2001, and were studied using restriction fragment length polymorphism (RFLP) and polymerase chain reaction (PCR)-RFLP. The major subgenus found was subgenus B (45%), followed by subgenus E (29%) and subgenus C (25%). Ad3 and Ad7 were the major types found during the 1st outbreak, which occurred from November 1999 to March 2000, while Ad4 was found mainly during the 2nd and 3rd outbreaks in October 2000 and September 2001, respectively. Both Ad7 and Ad4 were reemerged serotypes, whereas Ad3 was consistently isolated during the survey, although it declined drastically from 36 to 2% in 2001. Genotype analysis in this study showed that the only strain of Ad7 found in 1983 was Ad7a, but all randomly selected strains of Ad7 isolated during 1999-2000 were Ad7b. The clinical features of 217 patients were analyzed during the 1999-2000 outbreaks. About 79% of the total cases were less than 7 years old. The ratio of male to female was 2:1. Severe infections, such as pneumonia and acute bronchitis, accounted for nearly half of the cases (43%). These results show the reemergence and changing of serotypes, the clinical association of respiratory adenovirus infections, and the molecular epidemiology of Ad7 genotypes in Taiwan during the past two decades.
Journal of Medical Virology 07/2004; 73(2):274-9. · 2.37 Impact Factor