The structure of an insect parvovirus (Galleria mellonella densovirus) at 3.7 å resolution

Simpson, A.A.; Chipman, Paul R.; Baker, Timothy S.; Tijssen, Peter; Rossmann, Michael G.

doi:10.1016/s0969-2126(98)00136-1

Cited by 109 publications

(121 citation statements)

References 40 publications

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“…The first few parvovirus capsid structures to be solved were the canine parvovirus [Tsao, J et al, 1991], followed by feline panleukopenia virus [Agbandje, M et al, 1993], B19 [Chipman, PR et al, 1996;Kaufmann, B et al, 2004], the minute virus of mice (MVM) [Llamas-Saiz, AL, 1997] and Galleria mellonella densovirus [Simpson, AA et al, 1998]. The structural details from these parvovirus capsids have been used as a foundation for many AAV studies because of their structural similarity in several domains.…”

Section: Capsid Crystal Structure: So Much To Learnmentioning

confidence: 99%

AAV Hybrid Serotypes: Improved Vectors for Gene Delivery

Choi¹,

McCarty²,

Samulski³

2005

CGT

163

128

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In recent years, significant efforts have been made on studying and engineering adeno-associated virus (AAV) capsid, in order to increase efficiency in targeting specific cell types that are nonpermissive to wild type (wt) viruses and to improve efficacy in infecting only the cell type of interest. With our previous knowledge of the viral properties of the naturally occurring serotypes and the elucidation of their capsid structures, we can now generate capsid mutants, or hybrid serotypes, by various methods and strategies. In this review, we summarize the studies performed on AAV retargeting, and categorize the available hybrid serotypes to date, based on the type of modification: 1) transcapsidation, 2) adsorption of bi-specific antibody to capsid surface, 3) mosaic capsid, and 4) chimeric capsid. Not only these hybrid serotypes could achieve high efficiency of gene delivery to a specific targeted cell type, which can be better-tailored for a particular clinical application, but also serve as a tool for studying AAV biology such as receptor binding, trafficking and genome delivery into the nucleus. Keywords

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Section: Capsid Crystal Structure: So Much To Learnmentioning

confidence: 99%

AAV Hybrid Serotypes: Improved Vectors for Gene Delivery

Choi¹,

McCarty²,

Samulski³

2005

CGT

163

128

View full text Add to dashboard Cite

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“…Capsid structures of various parvoviruses have been resolved by X-ray crystallography or electron cryomicroscopy (1,2,3,37,40,42,59,66,71,79,83,84). All of these particles show similar structural arrangements at the inner surface.…”

mentioning

confidence: 99%

Mutational Analysis of Narrow Pores at the Fivefold Symmetry Axes of Adeno-Associated Virus Type 2 Capsids Reveals a Dual Role in Genome Packaging and Activation of Phospholipase A2 Activity

Bleker

Sonntag

Kleinschmidt

2005

J Virol

159

185

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Adeno-associated virus type 2 (AAV2) capsids show 12 pores at the fivefold axes of symmetry. We mutated amino acids which constitute these pores to investigate possible functions of these structures within the AAV2 life cycle. Mutants with alterations in conserved residues were impaired mainly in genome packaging or infectivity, whereas few mutants were affected in capsid assembly. The packaging phenotype was characterized by increased capsid-per-genome ratios. Analysis of capsid-associated DNA versus encapsidated DNA revealed that this observation was due to reduced and not partial DNA encapsidation. Most mutants with impaired infectivity showed a decreased capability to expose their VP1 N termini. As a consequence, the activation of phospholipase A2 (PLA2) activity, which is essential for efficient infection, was affected on intact capsids. In a few mutants, the exposure of VP1 N termini and the development of PLA2 activity were associated with enhanced capsid instability, which is obviously also deleterious for virus infection. Therefore, PLA2 activity seems to be required on intact capsids for efficient infection. In conclusion, these results suggest that the pores at the fivefold axes function not only as portals for AAV2 single-stranded DNA packaging but also as channels for presentation of the PLA2 domain on AAV2 virions during infection.The viral capsid can be considered as a multiprotein complex which not only protects the viral genome against extreme environmental influences outside the cell but also combines a number of functional elements which are needed for host cell recognition, intracellular trafficking, and disassembly in order to successfully deliver genetic information to the host cell (for reviews, see references 23, 60, and 75). These functional elements either are concomitantly transported with the virion as separate proteins or are part of the structural proteins themselves. Identifying such functional elements on viral capsids is one of the most attractive goals of viral structural research. Over the past few years, several such functional domains have been identified in parvoviruses (for a review, see reference 70).Adeno-associated virus (AAV) type 2 (AAV2) is a member of the parvovirus family. AAV2 requires coinfection with helper viruses, such as adenovirus or herpesvirus, for efficient reproduction (4, 9, 58) and has a nonenveloped icosahedral capsid. It encloses a 4.7-kb single-stranded DNA (ssDNA) genome containing two large open reading frames, rep and cap (61). The Rep proteins, encoded by the rep gene, are required for DNA replication, DNA encapsidation, and control of gene expression (36,45). The viral capsid is composed of three structural viral proteins (VPs), designated VP1, VP2, and VP3, which are encoded by the cap open reading frame and expressed from the p40 promoter. Capsids are formed with the VPs in an approximate molar ratio of 1:1:10 due to alternative splicing and an unconventional start codon for VP2. This ratio is also maintained in assembled capsids (6, 34). The ...

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“…The observations that parvoviruses replicate in the nucleus, closely in tune with the physiology of the host cell, and are able to do so with both vertebrate and invertebrate cells, suggest that vertebrate and invertebrate parvoviruses may be more different than usually accepted. Indeed, when recently the first 3D structure of an invertebrate parvovirus was solved by X-ray crystallography (Simpson et al, 1998), major differences were observed between the two virus groups. Despite many differences in the molecular biology of these virus groups, it is surprising how many aspects of their genome organization and molecular biology are shared, justifying their classification as one family.…”

Section: Tijssenmentioning

confidence: 99%

“…The 3D structures of several vertebrate parvoviruses (CPV, FPV, MVM) and, recently, of an invertebrate parvovirus (GmDNV) have been solved to nearatomic resolution using X-ray crystallography (Simpson et al, 1998). All have a common structure arranged with T = 1 icosahedral symmetry with each subunit having the same eight-stranded anti-parallel >-barrel motif (Fig.…”

Section: Three-dimensional Structure Of Parvovirusesmentioning

confidence: 99%

Molecular and Structural Basis of the Evolution of Parvovirus Tropism

Tijssen¹

1999

Acta Veterinaria Hungarica

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The structure of an insect parvovirus (Galleria mellonella densovirus) at 3.7 å resolution

Cited by 109 publications

References 40 publications

AAV Hybrid Serotypes: Improved Vectors for Gene Delivery

AAV Hybrid Serotypes: Improved Vectors for Gene Delivery

Mutational Analysis of Narrow Pores at the Fivefold Symmetry Axes of Adeno-Associated Virus Type 2 Capsids Reveals a Dual Role in Genome Packaging and Activation of Phospholipase A2 Activity

Molecular and Structural Basis of the Evolution of Parvovirus Tropism

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