Phylogeography of Coxsackievirus A16 Reveals Global Transmission Pathways and Recent Emergence and Spread of a Recombinant Genogroup (original) (raw)
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Molecular phylogeny of modern coxsackievirus A16
Archives of Virology, 2007
A phylogenetic analysis of VP1 and VP4 nucleotide sequences of 52 recent CVA16 strains demonstrated two distinct CVA16 genogroups, A and B, with the prototype strain being the only member of genogroup A. CVA16 G-10, the prototype strain, showed a nucleotide difference of 27.7-30.2% and 19.9-25.2% in VP1 and VP4, respectively, in relation to other CVA16 strains, which formed two separate lineages in genogroup B with nucleotide variation of less than 13.4% and less than 16.3% in VP1 and VP4, respectively. Lineage 1 strains circulating before 2000 were later displaced by lineage 2 strains. Ã Hand, foot, and mouth disease (HFMD) is a common febrile illness of children associated with infections of species A enteroviruses from the genus Enterovirus within the family Picornaviridae. Lesions on the skin and oral mucosa typically characterize the illness, with herpangina also presented in some patients. Several enterovirus serotypes have been associated with this disease, the majority of these being members of human enterovirus A, such as coxsackieviruses (CV) A2, A4, A5, A8, A10, A16 and human enterovirus (HEV) 71 . Of these, CVA16 and HEV71 are the major causative agents associated with HFMD, and co-circulation of both of these serotypes during outbreaks of HFMD
Spatiotemporal phylogenetic analysis and molecular characterization of coxsackievirus A4
Infection Genetics and Evolution, 2011
Coxsackievirus A4 (CV-A4) Human enterovirus A (HEV-A) Spatiotemporal phylogenetic analysis Molecular epidemiology Taiwan A B S T R A C T Coxsackievirus A4 outbreaks occurred in Taiwan in 2004 and 2006. The spatiotemporal transmission of this error-prone RNA virus involves a continuous interaction between rapid sequence variation and natural selection. To elucidate the molecular characteristics of CV-A4 and the spatiotemporal dynamic changes in CV-A4 transmission, worldwide sequences of the 3 0 VP1 region (420 nt) obtained from GenBank were analyzed together with sequences isolated in Taiwan from 2002 to 2009. Sequences were characterized in terms of recombination, variability, and selection. Phylogenetic trees were constructed using neighbor-joining, maximum likelihood and Monte Carlo Markov Chain methods. Spatiotemporal dynamics of CV-A4 transmission were further estimated by a Bayesian statistical inference framework. No recombination was detected in the 420 nt region. The estimated evolution rate of CV-A4 was 8.65 Â 10 À3 substitutions/site/year, and a purifying selection (d N /d S = 0.032) was noted over the 3 0 VP1 region. All trees had similar topology: two genotypes (GI and GII), each including two subgenotypes (A and B), with the prototype and a Kenyan strain in separate branches. The results revealed that the virus first appeared in USA in 1950. Since 1998, it has evolved into the Kenya, GI-A (Asia) and GII-A (Asia and Europe) strains. Since 2004, GI-B and GII-B have evolved continuously and have remained prevalent. The co-existence of several positive selection lineages of GI-B in 2006 indicates that the subgenotype might have survived lineage extinction. This study revealed rapid lineage turnover of CV-A4 and the replacement of previously circulating strains by a new dominant variant. Therefore, continuous surveillance for further CV-A4 transmission is essential. ß
Complete Genome Sequences of Three Strains of Coxsackievirus A7
Genome Announcements, 2013
Genomes of three strains (Parker, USSR, and 275/58) of coxsackievirus A7 (CV-A7) were amplified by the long reverse transcription (RT)-PCR method and sequenced. While the sequences of Parker and USSR were identical, the similarities of 275/58 to the CV-A7 reference sequence, accession no. AY421765, were 82.6% and 96.2% for nucleotides and amino acids, respectively.
Microbiology and Immunology, 2013
To clarify the longitudinal molecular epidemiology of coxsackievirus A16, phylogenetic analysis based on the VP1 region of 220 isolates in Yamagata, Japan was performed. The resultant phylogenetic tree indicates that the Yamagata isolates and reference strains can be readily genotyped into three genogroups, and 0, 12 and 208 isolates belonged to the first, second, and third genogroups, respectively. The first genogroup includes only the prototype strain, the second strains that had disappeared by the end of the 20th century and the third comprises those that have been circulating since then in local communities, such as Yamagata.
Virus Research, 1999
The full length sequence for the human pathogen coxsackievirus B6 (CVB6, Schmitt strain) has been determined. We used long RT-PCR to generate full length DNA amplicon of CVB6, and then directly sequenced the amplicons. One-step cloning of the full length amplicon enabled us to obtain an infectious clone of CVB6. RNA generated from CVB6 amplicon DNA or CVB6 clones, by transcription with T7 RNA polymerase, was demonstrated to be infectious upon transfection into HeLa cells in vitro. The CVB6 genome is characteristic of enteroviruses, with a 5%-non-translated region (743 nucleotides) followed by an open reading frame (encoding a 2184 amino acid polyprotein) and a 3%-non-translated region (100 nucleotides) and polyadenylated tail. The predicted amino acid sequence of CVB6 clustered with the other CVB serotypes and swine vesicular disease virus (SVDV).
Molecular evolution of coxsackievirus A24v in Cuba over 23-years, 1986–2009
Scientific Reports
Coxsackievirus A24 variant (CVA24v) is a major causative agent of acute hemorrhagic conjunctivitis outbreaks worldwide, yet the evolutionary and transmission dynamics of the virus remain unclear. To address this, we analyzed and compared the 3C and partial VP1 gene regions of CVA24v isolates obtained from five outbreaks in Cuba between 1986 and 2009 and strains isolated worldwide. Here we show that Cuban strains were homologous to those isolated in Africa, the Americas and Asia during the same time period. Two genotypes of CVA24v (GIII and GIV) were repeatedly introduced into Cuba and they arose about two years before the epidemic was detected. The two genotypes co-evolved with a population size that is stable over time. However, nucleotide substitution rates peaked during pandemics with 4.39 × 10 −3 and 5.80 × 10 −3 substitutions per site per year for the 3C and VP1 region, respectively. The phylogeographic analysis identified 25 and 19 viral transmission routes based on 3C and VP1 regions, respectively. Pandemic viruses usually originated in Asia, and both China and Brazil were the major hub for the global dispersal of the virus. Together, these data provide novel insight into the epidemiological dynamics of this virus and possibly other pandemic viruses. Human enteroviruses are small, non-enveloped viruses belonging to the Enterovirus genus of the Picornaviridae family 1. The genome is a single-stranded positive sense RNA molecule of approximately 7.4 kb and possesses a long open reading frame (ORF) that is flanked on both ends by the 5′ and 3′ untranslated regions. The ORF encodes a polyprotein, which is cleaved to form seven non-structural proteins (2A, 2B, 2C, 3A, 3B, 3C, and 3D) and four structural proteins (VP1, VP2, VP3, and VP4). Human enteroviruses comprise four species, namely, species Enterovirus A-Enterovirus D. Each of these four species is formed by five to 63 different types, with no cross neutralization, i.e. infection with one type does not infer immunity against another type 1. Recombination has often been reported either between members of the same or different human enteroviruses species. The recombination "hotspot" regions are located not only between the structural and non-structural coding regions but also between the 5′ non-coding region and the protein-encoding region of human enteroviruses 2. Coxsackievirus A24v (CVA24v), an antigenic variant of the CVA24 strain (member of species Enterovirus C), was first isolated from an outbreak of acute hemorrhagic conjunctivitis (AHC) in Singapore in 1970. Afterwards, CVA24v has been identified as the major causative agent of AHC outbreaks worldwide 3-5. Currently, four genotypes of CVA24v have been described (I-IV), which have been responsible for major global epidemics of AHC 5-7. Several studies have investigated the genetic diversity and molecular evolution of CVA24v strains during periods varying from 4 to 20 years 5-7. Most of these studies were performed on strains of CVA24v that
Transmission and Demographic Dynamics of Coxsackievirus B1
PLOS ONE, 2015
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 3D pol (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 3D pol 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 PLOS ONE |
Characterization of a Putative Ancestor of Coxsackievirus B5
Journal of Virology, 2010
Like other RNA viruses, coxsackievirus B5 (CVB5) exists as circulating heterogeneous populations of genetic variants. In this study, we present the reconstruction and characterization of a probable ancestral virion of CVB5. Phylogenetic analyses based on capsid protein-encoding regions (the VP1 gene of 41 clinical isolates and the entire P1 region of eight clinical isolates) of CVB5 revealed two major cocirculating lineages. Ancestral capsid sequences were inferred from sequences of these contemporary CVB5 isolates by using maximum likelihood methods. By using Bayesian phylodynamic analysis, the inferred VP1 ancestral sequence dated back to 1854 (1807 to 1898). In order to study the properties of the putative ancestral capsid, the entire ancestral P1 sequence was synthesized de novo and inserted into the replicative backbone of an infectious CVB5 cDNA clone. Characterization of the recombinant virus in cell culture showed that fully functional infectious virus particles were assembled and that these viruses displayed properties similar to those of modern isolates in terms of receptor preferences, plaque phenotypes, growth characteristics, and cell tropism. This is the first report describing the resurrection and characterization of a picornavirus with a putative ancestral capsid. Our approach, including a phylogenetics-based reconstruction of viral predecessors, could serve as a starting point for experimental studies of viral evolution and might also provide an alternative strategy for the development of vaccines.
Viruses
Coxsackievirus A16 (CVA16) is well known for causing hand-foot-and-mouth disease (HFMD) and outbreaks were frequently reported in Taiwan in the past twenty years. The epidemiology and genetic variations of CVA16 in Taiwan from 1998 to 2021 were analyzed in this study. CVA16 infections usually occurred in early summer and early winter, and showed increased incidence in 1998, 2000–2003, 2005, 2007–2008, and 2010 in Taiwan. Little or no CVA16 was detected from 2017 to 2021. CVA16 infection was prevalent in patients between 1 to 3 years old. A total of 69 isolates were sequenced. Phylogenetic analysis based on the VP1 region showed that CVA16 subgenotype B1 was dominantly isolated in Taiwan from 1998 to 2019, and B2 was identified only from isolates collected in 1999 and 2000. There was a high frequency of synonymous mutations in the amino acid sequences of the VP1 region among CVA16 isolates, with the exception of position 145 which showed positive selection. The recombination analysis...