Emerging Human Parvoviruses: The Rocky Road to Fame

Söderlund‐Venermo, Maria

doi:10.1146/annurev-virology-092818-015803

Cited by 36 publications

(31 citation statements)

References 154 publications

(307 reference statements)

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“…Adeno-Associated Viruses (AAVs) are small, non-enveloped viruses that hold great promise as gene therapy vectors [1]. AAVs belong to the genus dependoparvovirus ,in the family Parvovirinae (for reviews, [2][3][4]). The model species is dependoparvovirus A, of which the prototype strain is AAV2.…”

Section: Introductionmentioning

confidence: 99%

Sequence Properties of the MAAP Protein and of the VP1 Capsid Protein of Adeno-Associated Viruses

Karlin¹

2020

Preprint

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Adeno-associated viruses (AAVs, genus dependoparvovirus) are promising gene therapy vectors. In strains AAV1-12, the capsid gene VP1 encodes a recently discovered protein, MAAP, in an overlapping frame.MAAP binds the cell membrane by an unknown mechanism. We discovered that MAAP is also encoded in bovine AAV and in porcine AAVs (which have shown promise for gene transfer into muscle tissues), in which it is probably translated from a non-canonical start codon. MAAP is predicted to be mostly disordered except for a predicted C-terminal, membrane-binding amphipathic α-helix. MAAP has a highly unusual composition. In particular, it lacks internal methionines, and is devoid of tyrosines in most strains.Unexpectedly, we discovered that the N-terminus of VP1 also lacks several amino acids. In all AAVs that encode MAAP, the first 200 aas of VP1 are devoid of internal methionines, probably owing to a selection against ATG codons that could prevent translation of MAAP and of capsid isoforms (VP2, VP3). The Nterminus of VP1 also lacks cysteines, likely to avoid the formation of disulfide bridges when it becomes exposed outside of the capsid during post-endocytic trafficking. Finally, the region common to VP1 and VP2 lacks tyrosine in the vast majority of AAVs that encode MAAP. Avoiding these "forbidden" aas in MAAP and VP1 when creating recombinant AAV capsids might increase the efficiency of capsid design. Conversely, the presence of "forbidden" aas in some rare strains probably indicates that they have unusual properties that could help us understand the viral cycle.Preprints (www.preprints.org) | NOT PEER-REVIEWED |

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Section: Introductionmentioning

confidence: 99%

Sequence Properties of the MAAP Protein and of the VP1 Capsid Protein of Adeno-Associated Viruses

Karlin¹

2020

Preprint

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“…In this study, the PARV4 sequences in two PARV4‐DNA positive source plasma pool samples were genotyped and the results demonstrated that at least two PARV4 genotypes, 1 and 2, were currently present in China. No genotype 3 was detected, which was not unexpected since this genotype was reported to be endemic in Ghana 16 . Besides, the possibility that genotype 3 might be present at an extremely low level in the sample, and, therefore, escaped identification can not be completely ruled out.…”

Section: Discussionmentioning

confidence: 70%

“…All these three genotypes have been detected in human blood or blood products although they seem to have different epidemiology. Genotypes 1 and 2 are prevalent in North America, Europe, and some countries in Asia while genotype 3 seems to be endemic in Ghana 16 . However, data on the existence of different PARV4 genotypes circulating in Chinese plasma donors are limited.…”

Section: Introductionmentioning

confidence: 99%

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Identification of human parvovirus 4 genotypes 1 and 2 in Chinese source plasma pools

Jia

Zhong

Zhang

et al. 2021

Journal of Medical Virology

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Human parvovirus B19 (B19V) and human parvovirus 4 (PARV4) are known to infect humans and transmit through contaminated blood and blood products. Globally, three genotypes of B19V, as well as PARV4, have been identified, respectively. The existence of different B19V genotypes in Chinese plasma donors has been investigated, however, the data regarding PARV4 were not available. The main objective of this study is to identify the genotypes of PARV4 circulating in Chinese plasma donors. By using a duplex quantitative polymerase chain reaction assay adapted for all genotypes of B19V and PARV4, 78 source plasma pools for fractionation were screened and quantified. Results showed that positive rates of B19V and PARV4 DNA in plasma pool samples were 25.64% and 14.10%, respectively. PARV4 sequences in two positive samples were next genotyped, and these two sequences belonged to PARV4 genotypes 1 and 2, respectively. In conclusion, the data present demonstrate the existence of PARV4 genotypes 1 and 2 in Chinese plasma donors for the first time and also show the relatively lower prevalence and level of PARV4 DNA in Chinese plasma donors in comparison with that of B19V DNA.

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“…Parvoviruses are small, non-enveloped viruses (for reviews, see [1][2][3]). We will focus on two in particular: human parvovirus B19 (B19V) and human parvovirus 4 (PARV4).…”

Section: Introductionmentioning

confidence: 99%

Parvovirus B19 and Human Parvovirus 4 Encode a Homologous "X Protein" in a Reading Frame Overlapping the VP1 Capsid Gene

Karlin¹

2020

Preprint

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30 years ago, researchers noticed that the capsid (VP1) gene of B19 parvovirus might encode a second protein, called "X", in an overlapping reading frame. Since then, experimental approaches failed to detect it. In contrast, sequence analyses can reliably predict whether a protein is expressed from an overlapping frame, provided that it is beneficial to the virus and thus under selection pressure. We used a dedicated software, Synplot2, to identify regions of VP1 likely to encode functional proteins in overlapping frames. Synplot2 detected the X open reading frame and confirmed it is under highly significant selection pressure. We discovered that the X protein is homologous to the ARF1 protein of human parvovirus 4, another suspected protein encoded in a frame overlapping VP1. These findings provide compelling evidence that the X protein must be expressed and functional. We predict that it contains a predicted transmembrane region. We found that the X frame contains a potential AUG start codon in parvovirus B19 and in all related species. Yet no currently known viral transcript has the potential to encode the X protein in a monocistronic fashion. Therefore, the X protein is probably expressed either from an unmapped monocistronic mRNA, or translated by a non-canonical mechanism from the VP1 mRNA or from a short transcript, R3, which has no currently known function. Finally, Synplot2 also detected proteins likely to be expressed from a frame overlapping VP1 in species distantly related to parvovirus B19: porcine parvovirus 2 and bovine parvovirus 3.

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Emerging Human Parvoviruses: The Rocky Road to Fame

Cited by 36 publications

References 154 publications

Sequence Properties of the MAAP Protein and of the VP1 Capsid Protein of Adeno-Associated Viruses

Sequence Properties of the MAAP Protein and of the VP1 Capsid Protein of Adeno-Associated Viruses

Identification of human parvovirus 4 genotypes 1 and 2 in Chinese source plasma pools

Parvovirus B19 and Human Parvovirus 4 Encode a Homologous "X Protein" in a Reading Frame Overlapping the VP1 Capsid Gene

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