Evolutionary Genetics of Human Enterovirus 71: Origin, Population Dynamics, Natural Selection, and Seasonal Periodicity of the VP1 Gene

Tee, Kok Keng; Lam, Tommy Tsan-Yuk; Chan, Yoke Fun; Bible, Jon M.; Kamarulzaman, Adeeba; Tong, C. Y. William; Takebe, Yutaka; Pybus, Oliver G.

doi:10.1128/jvi.01019-09

Cited by 202 publications

(226 citation statements)

References 80 publications

(79 reference statements)

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“…3D). This region at the 5-fold vertex represents a functional "hot spot," since these residues have been implicated in receptor binding and have been shown to determine virus virulence and affect positive selection (4,(10)(11)(12)18).…”

Section: Resultsmentioning

confidence: 99%

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Structures of the Procapsid and Mature Virion of Enterovirus 71 Strain 1095

Cifuente

Lee

Yoder

et al. 2013

J Virol

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bEnterovirus 71 (EV71) is an important emerging human pathogen with a global distribution and presents a disease pattern resembling poliomyelitis with seasonal epidemics that include cases of severe neurological complications, such as acute flaccid paralysis. EV71 is a member of the Picornaviridae family, which consists of icosahedral, nonenveloped, single-stranded RNA viruses. Here we report structures derived from X-ray crystallography and cryoelectron microscopy (cryo-EM) for the 1095 strain of EV71, including a putative precursor in virus assembly, the procapsid, and the mature virus capsid. The cryo-EM map of the procapsid provides new structural information on portions of the capsid proteins VP0 and VP1 that are disordered in the higher-resolution crystal structures. Our structures solved from virus particles in solution are largely in agreement with those from prior X-ray crystallographic studies; however, we observe small but significant structural differences for the 1095 procapsid compared to a structure solved in a previous study (

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Section: Resultsmentioning

confidence: 99%

“…The mature capsid is built of 60 structural subunits or protomers, which are comprised of four structural proteins, VP1 to VP4 (VP1-4). Several key residues that map to the 5-fold symmetry vertex, VP1 98 and 145, have been linked to positive selection, virulence, and receptor binding (4,(10)(11)(12).…”

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confidence: 99%

Structures of the Procapsid and Mature Virion of Enterovirus 71 Strain 1095

Cifuente

Lee

Yoder

et al. 2013

J Virol

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“…6) (16, 22). VP1-145 has been found to be under positive selection (36,37) and has been implicated as one of the possible determinants of virulence in humans (38,39) and adaptation in the mouse (40)(41)(42). It is likely that the EV71 antigenicity, as well as receptor-binding phenotype, is altered with a single mutation at VP1-145, which may confer an advantage to EV71 for effective host infection and transmission.…”

Section: Discussionmentioning

confidence: 99%

A Strain-Specific Epitope of Enterovirus 71 Identified by Cryo-Electron Microscopy of the Complex with Fab from Neutralizing Antibody

Lee

Cifuente

Ashley

et al. 2013

J Virol

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e Enterovirus 71 (EV71) is a picornavirus that causes outbreaks of hand, foot, and mouth disease (HFMD), primarily in the Asia-Pacific area. Unlike coxsackievirus A16, which also causes HFMD, EV71 induces severe neuropathology leading to high fatalities, especially among children under the age of 6 years. Currently, no established vaccines or treatments are available against EV71 infection. The monoclonal antibody MA28-7 neutralizes only specific strains of EV71 that have a conserved glycine at amino acid VP1-145, a surface-exposed residue that maps to the 5-fold vertex and that has been implicated in receptor binding. The cryo-electron microscopy structure of a complex between EV71 and the Fab fragment of MA28-7 shows that only one Fab fragment occupies each 5-fold vertex. A positively charged patch, which has also been implicated in receptor binding, lies within the Fab footprint. We identify the strain-specific epitope of EV71 and discuss the possible neutralization mechanisms of the antibody. E nterovirus 71 (EV71) infection causes outbreaks of hand, foot, and mouth disease (HFMD), predominantly in the Asia-Pacific region (1, 2). Whereas most EV71 infections are self-limiting, neurological and systemic complications can develop that range from aseptic meningitis to encephalitis and acute flaccid paralysis. Infection can lead to lethal pulmonary edema and heart failure (2), with mortality being especially high in young children under the age of 6 (2, 3). As seasonal outbreaks of HFMD are recurring around the world, development of a vaccine and antiviral therapies for EV71 has become an urgent concern.A member of the Picornaviridae family, EV71 has a nonenveloped, icosahedral capsid comprised of 60 copies of each of four viral structural proteins (VP1 to VP4) (4). Recent studies have solved the structures for three strains of EV71 (MY104 [5], Fuyang [6], and 1095 [7]), demonstrating that EV71 has the general features of picornavirus capsids, including the 5-fold "mesa" and the depression around the mesa called the "canyon" (5-8). Conserved residues VP1-242K and VP1-244K form positively charged patches on the 5-fold mesa (6), and this symmetry-related clustering of positive charges has been suggested as a common mechanism for heparan sulfate binding in enteroviruses (9).Several cellular receptors for EV71 have been identified: scavenger receptor B2 (SCARB2), P-selectin glycoprotein ligand-1 (PSGL-1), and heparan sulfate (HS) (10-12). SCARB2, which is expressed on a broad variety of cell types, likely binds to the virus canyon and induces the transition of the virion that is required for uncoating (13-15). PSGL-1, which is expressed exclusively on lymphocytes, binds only specific EV71 strains and supports viral replication in lymphocytes in a PSGL-1-dependent manner (11). According to recent studies, PSGL-1 and HS bind the positively charged patches on the 5-fold mesa of EV71 and provide initial attachment on the cell (12,16,17). We recently found that the PSGL-1 binding phenotype of EV71 strains is regulated b...

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“…The evolutionary history of EV-71 is characterized by two dissemination waves of genetically distinct populations: the first occurred with the spread of genogroup B viruses, while the second happened only 40 years ago and resulted from the dissemination of (Tee et al, 2010). Despite a different number of sequences compiled for each genogroup and the low nucleotide polymorphism for the 1D and 3CD loci, Bayesian analyses gave confident phylogenies.…”

Section: Consistent Phylogenies Of Circulating Ev-71 Strains Obtainedmentioning

confidence: 99%

Phylogenetic evidence for a recent spread of two populations of human enterovirus 71 in European countries

Mirand

Schuffenecker

Henquell

et al. 2010

Journal of General Virology

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Human enterovirus 71 (EV-71) is a cause of seasonal epidemics of hand, foot and mouth disease, and of less common but severe neurological manifestations. Uncertainty persists regarding the circulation of virus populations in several geographical areas and the timescale of their dissemination. We determined EV-71 sequences at loci 1D (VP1 capsid protein) and 3CD (nonstructural proteins) in 86 strains recovered in Austria, France and Germany and performed an evolutionary genetic study of extant virus populations. Phylogenetic analyses positioned 78 of the 86 sequences within two clades among subgenogroups C1 and C2. A minor sequence cluster was assigned to subgenogroup C4. Analyses incorporating the available sequences estimated the substitution rate in genogroup C at 3.66¾10 "3 and 4.46¾10 "3 substitutions per site year "1 for loci 1D and 3CD, respectively, assuming a relaxed molecular-clock model for sequence evolution. Most of the 'European' strains belonged to clades C1b and C2b, which originated in 1994 [95 % confidence interval (CI), 1992.7"1995.8] and 2002 (95 % CI, 2001.6"2003, respectively. Estimates of divergence times for locus 3CD were consistent with those measured for locus 1D. Intertwining between clades representing EV-71 subgenogroups and clades corresponding to other enterovirus types (notably early coxsackievirus A prototype strains) in the 3CD phylogeny is highly indicative of ancestral recombination events. Incongruent phylogenetic patterns estimated for loci 1D and 3CD show that a single tree cannot model the epidemic history of circulating EV-71 populations. The evolutionary timescale of genogroup C estimated for both loci was measured only in decades, indicating recent dissemination.

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Evolutionary Genetics of Human Enterovirus 71: Origin, Population Dynamics, Natural Selection, and Seasonal Periodicity of the VP1 Gene

Cited by 202 publications

References 80 publications

Structures of the Procapsid and Mature Virion of Enterovirus 71 Strain 1095

Structures of the Procapsid and Mature Virion of Enterovirus 71 Strain 1095

A Strain-Specific Epitope of Enterovirus 71 Identified by Cryo-Electron Microscopy of the Complex with Fab from Neutralizing Antibody

Phylogenetic evidence for a recent spread of two populations of human enterovirus 71 in European countries

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