RESUMO
Structural studies of foot-and-mouth disease virus (FMDV) have largely focused on the mature viral particle, providing atomic resolution images of the spherical protein capsid for a number of sero- and sub-types, structures of the highly immunogenic surface loop, Fab and GAG receptor complexes. Additionally, structures are available for a few non-structural proteins. The chapter reviews our current structural knowledge and its impact on our understanding of the virus life cycle proceeding from the mature virus through immune evasion/inactivation, cell-receptor binding and replication and alludes to future structural targets.
Assuntos
Vírus da Febre Aftosa/química , Vírus da Febre Aftosa/ultraestrutura , Proteínas do Capsídeo/química , Genoma Viral , Proteoglicanas de Heparan Sulfato/metabolismo , Integrinas/metabolismo , Receptores Virais/metabolismo , Proteínas não Estruturais Virais/química , Montagem de VírusRESUMO
Virus crystallography can provide atomic resolution structures for intact isometric virus particles and components thereof. The methodology is illustrated by reference to a particularly complex example, the core of the bluetongue virus (700 A).
Assuntos
Vírus Bluetongue/química , Vírus Bluetongue/ultraestrutura , Microscopia Crioeletrônica , Cristalografia por Raios X , Proteínas do Core Viral/química , CristalizaçãoRESUMO
The complete genomic sequence of kelp fly virus (KFV), originally isolated from the kelp fly, Chaetocoelopa sydneyensis, has been determined. Analyses of its genomic and structural organization and phylogeny show that it belongs to a hitherto undescribed group within the picorna-like virus superfamily. The single-stranded genomic RNA of KFV is 11,035 nucleotides in length and contains a single large open reading frame encoding a polypeptide of 3,436 amino acids with 5' and 3' untranslated regions of 384 and 343 nucleotides, respectively. The predicted amino acid sequence of the polypeptide shows that it has three regions. The N-terminal region contains sequences homologous to the baculoviral inhibitor of apoptosis repeat domain, an inhibitor of apoptosis commonly found in animals and in viruses with double-stranded DNA genomes. The second region contains at least two capsid proteins. The third region has three sequence motifs characteristic of replicase proteins of many plant and animal viruses, including a helicase, a 3C chymotrypsin-like protease, and an RNA-dependent RNA polymerase. Phylogenetic analysis of the replicase motifs shows that KFV forms a distinct and distant taxon within the picorna-like virus superfamily. Cryoelectron microscopy and image reconstruction of KFV to a resolution of 15 A reveals an icosahedral structure, with each of its 12 fivefold vertices forming a turret from the otherwise smooth surface of the 20-A-thick capsid. The architecture of the KFV capsid is unique among the members of the picornavirus superfamily for which structures have previously been determined.
Assuntos
Dípteros/virologia , Genoma Viral , Vírus de Insetos/classificação , Picornaviridae/classificação , Sequência de Aminoácidos , Animais , Capsídeo/química , Capsídeo/ultraestrutura , Proteínas do Capsídeo/genética , Vírus de Insetos/genética , Vírus de Insetos/ultraestrutura , Dados de Sequência Molecular , Fases de Leitura Aberta/genética , Filogenia , Picornaviridae/genética , Picornaviridae/ultraestrutura , RNA Polimerase Dependente de RNA/genética , Alinhamento de Sequência , Análise de SequênciaRESUMO
Heparan sulfate has an important role in cell entry by foot-and-mouth disease virus (FMDV). We find that subtype O1 FMDV binds this glycosaminoglycan with a high affinity by immobilizing a specific highly abundant motif of sulfated sugars. The binding site is a shallow depression on the virion surface, located at the junction of the three major capsid proteins, VP1, VP2 and VP3. Two pre-formed sulfate-binding sites control receptor specificity. Residue 56 of VP3, an arginine in this virus, is critical to this recognition, forming a key component of both sites. This residue is a histidine in field isolates of the virus, switching to an arginine in adaptation to tissue culture, forming the high affinity heparan sulfate-binding site. We postulate that this site is a conserved feature of FMDVs, such that in the infected animal there is a biological advantage to low affinity, or more selective, interactions with glycosaminoglycan receptors.