Expression of Aleutian mink disease parvovirus capsid proteins in defined segments: localization of immunoreactive sites and neutralizing epitopes to specific regions

Bloom, Marshall E.; Martin, David; Oie, Katrina L.; Huhtanen, Mark E.; Costello, Frederick A.; Wolfinbarger, James B.; Hayes, Stanley F.; Agbandje‐McKenna, Mavis

doi:10.1128/jvi.71.1.705-714.1997

Cited by 29 publications

(20 citation statements)

References 58 publications

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“…The presence of a dominant linear epitope is in agreement with the study by Bloom et al . [24]. They located a major linear epitope between amino acids 430 and 525, and also found potential but weaker linear epitopes around presumed AMDV loops 1–3, similar to that found in this study (Fig.…”

Section: Discussionsupporting

confidence: 87%

“…The influence of mink genotype on the immunological recognition of different epitopes was not part of this study, but was investigated by Bloom et al . [24] who found that there was no difference when mink of different genotypes were compared.…”

Section: Discussionmentioning

confidence: 99%

“…A rabbit antiserum to purified maltose‐binding protein (MBP) was kindly donated by Dr Marshall E. Bloom (NIH, NIAID) [24].…”

Section: Methodsmentioning

confidence: 99%

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Epitope Mapping of Aleutian Mink Disease Parvovirus Virion Protein VP1 and 2

Costello¹,

Steenfos²,

Jensen³

et al. 1999

Scand J Immunol

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Six overlapping fragments of the Aleutian Mink Disease parvoVirus (AMDV) virion protein VP1 and 2 (VP1/2) gene were inserted into the expression vector pMAL-c2. Four of the clones carried large overlapping fragments covering the entire VP1/2 gene. The remaining two clones covered specifically chosen regions within the VP1/2 gene. Using a Western blotting detection system, sera from AMDV-infected mink were tested against the recombinant polypeptides. These studies showed reactions primarily directed against the two AMDV polypeptides ranging from amino acids 297 to 518. Weaker reactions against other regions of the VP1/2 were also observed. The small fusion protein designed to cover the presumed AMDV VP1/2 loop 4 was purified by affinity chromatography and used to develop solid-phase immunoassays. Twelve small synthetic peptides were constructed and used as inhibitors. A peptide covering amino acids S428 to T448 was shown to block the reactivity of a pool of positive mink sera, indicating the presence of one dominant linear epitope.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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Epitope Mapping of Aleutian Mink Disease Parvovirus Virion Protein VP1 and 2

Costello¹,

Steenfos²,

Jensen³

et al. 1999

Scand J Immunol

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show abstract

“…The majority of the other AAV epitopes include regions reported to play a role in cellular transduction (reviewed in reference 72). Interestingly, a hypervariable region, which includes residues 208 to 290 (VR-III and VR-IV) of AMDV, serves as a strain-specific epitope (pVP2d) distinguishing the nonpathogenic AMDV-G from the pathogenic AMDV-Utah I strain (73). These residues are localized to the 2-/5-fold wall and 3-fold shoulder of the capsid, similar to what was observed for the HBoV1 strain-specific footprint (Fig.…”

Section: Discussionsupporting

confidence: 63%

Mapping Antigenic Epitopes on the Human Bocavirus Capsid

Kailasan

Garrison

Ilyas

et al. 2016

J Virol

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Human bocaviruses (HBoV1 to -4) are emerging pathogens associated with pneumonia and/or diarrhea in young children. Currently, there is no treatment or vaccination, so there is a need to study these pathogens to understand their disease mechanisms on a molecular and structural level for the development of control strategies. Here, we report the structures of six HBoV monoclonal antibody (MAb) fragment complexes, HBoV1-15C6, HBoV2-15C6, HBoV4-15C6, HBoV1-4C2, HBoV1-9G12, and HBoV1-12C1, determined by cryo-electron microscopy and three-dimensional image reconstruction to 18.0-to 8.5-Å resolution. Of these, the 15C6 MAb cross-reacted with HBoV1, HBoV2, and HBoV4, while the 4C2, 12C1, and 9G12 MAbs recognized only HBoV1. Pseudoatomic modeling mapped the 15C6 footprint to the capsid surface DE and HI loops, at the 5-fold axis and the depression surrounding it, respectively, which are conserved motifs in Parvoviridae. The footprints for 4C2, 12C1, and 9G12 span the surface loops that assemble portions of the 2-/5-fold wall (a raised surface feature between the 2-fold and 5-fold axes of symmetry) and the shoulder of the 3-fold protrusions. The MAb footprints, cross reactive and strain specific, coincide with regions with high and low sequence/structural identities, respectively, on the capsid surfaces of the HBoVs and identify potential regions for the development of peptide vaccines for these viruses. IMPORTANCEHuman bocaviruses (HBoVs) may cause severe respiratory and gastrointestinal infections in young children. The nonenveloped parvovirus capsid carries determinants of host and tissue tropism, pathogenicity, genome packaging, assembly, and antigenicity important for virus infection. This information is currently unavailable for the HBoVs and other bocaparvoviruses. This study identifies three strain-specific antigenic epitopes on the HBoV1 capsid and a cross-reactive epitope on the HBoV1, HBoV2, and HBoV4 capsids using structures of capsid-antibody complexes determined using cryo-electron microscopy and image reconstruction. This is the first study to report the highly conserved parvovirus DE loop at the 5-fold axis as a determinant of antigenicity. Additionally, knowledge of the strain-specific and conserved antigenic epitopes of the bocaviruses can be instrumental in characterization of the virus life cycle, development of peptide vaccines, and generation of gene delivery vectors for cystic fibrosis given the strict tropism of HBoV1 for human airway epithelial cells.

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“…2A, 5C, and 7). This loop region is a determinant of antibody recognition for other parvoviruses such as adeno-associated virus (AAV), human parvovirus B19, and Aleutian mink disease parvovirus (30,(49)(50)(51). The loop that corresponds to VR-V displays significant differences at both the sequence and structure levels among all three viruses ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Structural Insights into Human Bocaparvoviruses

Mietzsch

Kailasan

Garrison

et al. 2017

J Virol

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Bocaparvoviruses are emerging pathogens of the Parvoviridae family. Human bocavirus 1 (HBoV1) causes severe respiratory infections and HBoV2 to HBoV4 cause gastrointestinal infections in young children. Recent reports of lifethreatening cases, lack of direct treatment or vaccination, and a limited understanding of their disease mechanisms highlight the need to study these pathogens on a molecular and structural level for the development of therapeutics. Toward this end, the capsid structures of HBoV1, HBoV3, and HBoV4 were determined to a resolution of 2.8 to 3.0 Å by cryo-electron microscopy and three-dimensional image reconstruction. The bocaparvovirus capsids, which display different tissue tropisms, have features in common with other parvoviruses, such as depressions at the icosahedral 2-fold symmetry axis and surrounding the 5-fold symmetry axis, protrusions surrounding the 3-fold symmetry axis, and a channel at the 5-fold symmetry axis. However, unlike other parvoviruses, densities extending the 5-fold channel into the capsid interior are conserved among the bocaparvoviruses and are suggestive of a genus-specific function. Additionally, their major viral protein 3 contains loops with variable regions at their apexes conferring capsid surface topologies different from those of other parvoviruses. Structural comparisons at the strain (HBoV) and genus (bovine parvovirus and HBoV) levels identified differences in surface loops that are functionally important in host/tissue tropism, pathogenicity, and antigenicity in other parvoviruses and likely play similar roles in these viruses. This study thus provides a structural framework to characterize determinants of host/tissue tropism, pathogenicity, and antigenicity for the development of antiviral strategies to control human bocavirus infections.IMPORTANCE Human bocaviruses are one of only a few members of the Parvoviridae family pathogenic to humans, especially young children and immunocompromised adults. There are currently no treatments or vaccines for these viruses or the related enteric bocaviruses. This study obtained the first high-resolution structures of three human bocaparvoviruses determined by cryo-reconstruction. HBoV1 infects the respiratory tract, and HBoV3 and HBoV4 infect the gastrointestinal tract, tissues that are likely targeted by the capsid. Comparison of these viruses provides information on conserved bocaparvovirus-specific features and variable regions resulting in unique surface topologies that can serve as guides to characterize HBoV determinants of tissue tropism and antigenicity in future experiments. Based on the comparison to other existing parvovirus capsid structures, this study suggests capsid regions that likely control successful infection, including determinants of receptor

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Expression of Aleutian mink disease parvovirus capsid proteins in defined segments: localization of immunoreactive sites and neutralizing epitopes to specific regions

Cited by 29 publications

References 58 publications

Epitope Mapping of Aleutian Mink Disease Parvovirus Virion Protein VP1 and 2

Epitope Mapping of Aleutian Mink Disease Parvovirus Virion Protein VP1 and 2

Mapping Antigenic Epitopes on the Human Bocavirus Capsid

Structural Insights into Human Bocaparvoviruses

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