Structural Characterization of Cuta- and Tusavirus: Insight into Protoparvoviruses Capsid Morphology

Mietzsch, Mario; McKenna, Robert; Väisänen, Elina; Yu, Jennifer C.; Ilyas, Maria; Hull, Joshua A.; Kurian, Justin; Smith, J. W. G.; Chipman, Paul R.; Lasanajak, Yi; Smith, David F.; Söderlund‐Venermo, Maria; Agbandje‐McKenna, Mavis

doi:10.3390/v12060653

Cited by 9 publications

(7 citation statements)

References 60 publications

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“…It has been shown that swapping out residues of the GH loop between two closely-related lepidopteran DVs (GmDV and Junonia coenia DV) results in mistargeted trafficking in their respective hosts [52]. As ZmBWV is the first capsid structure resolved within genus Blattambidensovirus , it becomes increasingly evident that DVs possess capsids differing significantly between genera, similarly to the genus-linked variability among Parvovirinae capsid structures [29, 53].…”

Section: Resultsmentioning

confidence: 99%

Identification by cryoEM of a densovirus causing mass mortality in mass-reared larval darkling beetles (Zophobas morio)

Pénzes

Kaelber

2022

Preprint

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A reared colony of larval superworms (Zophobas morio) experienced the swift and unexplained death of about 90% of its population. We isolated a high-abundance virus from dead larvae and, using cryoEM, identified it as a novel densovirus, which we name Zophobas morio black wasting virus (ZmBWV). Densoviruses (DVs) are small, ssDNA viruses of the family Parvoviridae that infect protostome and deuterostome invertebrates. The vast majority of DVs have been associated with severe pathology, especially in larval stage insects. By cryoEM we resolved the high-resolution capsid structure of this new DV at 2.9 Å resolution for the genome-packaging, infectious particles and at a resolution of 3.3 Å in case of the empty particles, both purified directly from the infected Z. morio larvae. The capsid structure of ZmBWV provides the first insights into the capsid morphology of a structurally previously-uncharacterized genus, Blattambidensovirus. Consequently, the ZmBWV capsid harbors a unique surface morphology within the family, yet shows the T=1 icosahedral symmetry, the eight-stranded jelly roll core, as well as general features of multimer interactions previously found typical of subfamily Densovirinae. Although we have not inoculated healthy larvae with ZmBWV, on the basis of its prodigious abundance in infected larvae and the prior probability of larval pathology with viruses of this subfamily, ZmBWV is the most probable cause of the observed mass mortality event.

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Section: Resultsmentioning

confidence: 99%

Identification by cryoEM of a densovirus causing mass mortality in mass-reared larval darkling beetles (Zophobas morio)

Pénzes

Kaelber

2022

Preprint

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“…The fused three-fold protrusions are caused by VR-VIII with its subloop leading towards the three-fold symmetry axis. Interestingly, the fused three-fold protrusions of the animal protoparvoviruses (e.g., CPV) are generated by the equivalent loop, though without any sequence similarity [ 10 ]. The small depression at the two-fold symmetry axis is the result of VR-VI covering most of the depression from both sides ( Figure 3 a, right panel).…”

Section: Resultsmentioning

confidence: 99%

“…They ranged from 13% (AMDV vs. PARV4) to 34% (AMDV vs. CPV) ( Figure 5 a). In a previous study characterizing distant members of the Protoparvovirus genus, even intra-genus capsid sequence identity was as low as 30% [ 10 ]. Thus, AMDV showed a close relationship to the Protoparvovirus genus (34% to CPV) and PARV4 showed a close relationship to the Erythroparvovirus genus (29% to B19).…”

Section: Resultsmentioning

confidence: 99%

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Capsid Structure of Aleutian Mink Disease Virus and Human Parvovirus 4: New Faces in the Parvovirus Family Portrait

Lakshmanan

Mietzsch

Ybargollin

et al. 2022

Viruses

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Parvoviruses are small, single-stranded DNA viruses with non-enveloped capsids. Determining the capsid structures provides a framework for annotating regions important to the viral life cycle. Aleutian mink disease virus (AMDV), a pathogen in minks, and human parvovirus 4 (PARV4), infecting humans, are parvoviruses belonging to the genera Amdoparvovirus and Tetraparvovirus, respectively. While Aleutian mink disease caused by AMDV is a major threat to mink farming, no clear clinical manifestations have been established following infection with PARV4 in humans. Here, the capsid structures of AMDV and PARV4 were determined via cryo-electron microscopy at 2.37 and 3.12 Å resolutions, respectively. Despite low amino acid sequence identities (10–30%) both viruses share the icosahedral nature of parvovirus capsids, with 60 viral proteins (VPs) assembling the capsid via two-, three-, and five-fold symmetry VP-related interactions, but display major structural variabilities in the surface loops when the capsid structures are superposed onto other parvoviruses. The capsid structures of AMDV and PARV4 will add to current knowledge of the structural platform for parvoviruses and permit future functional annotation of these viruses, which will help in understanding their infection mechanisms at a molecular level for the development of diagnostics and therapeutics.

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“…Fluorescent labeling of VLPs. Volumes of 300 to 500 ml of purified HBoV1, HBoV2, AAV2, and AAV5 VLPs (0.5 to 0.8 mg/ml) were labeled using the DyLight 488 antibody labeling kit (Thermo Fisher) as described previously (71). Unbound dye was removed by repeated dialysis.…”

Section: Methodsmentioning

confidence: 99%

pH-Induced Conformational Changes of Human Bocavirus Capsids

Luo¹,

Mietzsch²,

Chipman³

et al. 2021

J Virol

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Human bocavirus 1 (HBoV1) and HBoV2-4 infect children and immunocompromised individuals, resulting in respiratory and gastrointestinal infections, respectively. Using cryo-electron microscopy and image reconstruction, the HBoV2 capsid structure was determined to 2.7 Å resolution at pH 7.4 and compared to the previously determined HBoV1, HBoV3, and HBoV4 structures. Consistent with previous findings, surface variable region (VR) III of the capsid protein VP3, proposed as a host tissue-tropism determinant, was structurally similar among the gastrointestinal strains HBoV2-4, but differed from HBoV1 with its tropism for the respiratory tract. Towards understanding the entry and trafficking properties of these viruses, HBoV1 and HBoV2 were further analyzed as species representatives of the two HBoV tropisms. Their cell surface glycan-binding characteristics were analyzed, and capsid structures determined to 2.5-2.7 Å resolution at pH 5.5 and 2.6, conditions normally encountered during infection. The data showed that glycans with terminal sialic acid, galactose, GlcNAc or heparan sulfate moieties do not facilitate HBoV1 or HBoV2 cellular attachment. With respect to trafficking, conformational changes common to both viruses were observed at low pH conditions localized to the VP N-terminus under the 5-fold channel, in the surface loops VR-I and VR-V and specific side-chain residues such as cysteines and histidines. The 5-fold conformational movements provide insight into the potential mechanism of VP N-terminal dynamics during HBoV infection and side-chain modifications highlight pH-sensitive regions of the capsid. IMPORTANCE Human bocaviruses (HBoVs) are associated with disease in humans. However, the lack of an animal model and a versatile cell culture system to study their life cycle limits the ability to develop specific treatments or vaccines. This study presents the structure of HBoV2, at 2.7 Å resolution, determined for comparison to the existing HBoV1, HBoV3, and HBoV4 structures, to enable the molecular characterization of strain and genus-specific capsid features contributing to tissue tropism and antigenicity. Furthermore, HBoV1 and HBoV2 structures determined under acidic conditions provide insight into capsid changes associated with endosomal and gastrointestinal acidification. Structural rearrangements of the capsid VP N-terminus, at the base of the 5-fold channel, demonstrate a disordering of a “basket” motif as pH decreases. These observations begin to unravel the molecular mechanism of HBoV infection and provide information for control strategies.

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Structural Characterization of Cuta- and Tusavirus: Insight into Protoparvoviruses Capsid Morphology

Cited by 9 publications

References 60 publications

Identification by cryoEM of a densovirus causing mass mortality in mass-reared larval darkling beetles (Zophobas morio)

Identification by cryoEM of a densovirus causing mass mortality in mass-reared larval darkling beetles (Zophobas morio)

Capsid Structure of Aleutian Mink Disease Virus and Human Parvovirus 4: New Faces in the Parvovirus Family Portrait

pH-Induced Conformational Changes of Human Bocavirus Capsids

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