The Diversity of Parvovirus Telomeres

Abstract

Parvoviridae are small viruses composed of a 4–6 kb linear single-stranded DNA protected by an icosahedral capsid. The viral genes coding non-structural (NS), capsid, and accessory proteins are flanked by intriguing sequences, namely the telomeres. Telomeres are essential for parvovirus genome replication, encapsidation, and integration. Similar (homotelomeric) or different (heterotelomeric) at the two ends, they all contain imperfect palindromes that fold into hairpin structures. Up to 550 nucleotides in length, they harbor a wide variety of motifs and structures known to be recognized by host cell factors. Our study aims to comprehensively analyze parvovirus ends to better understand the role of these particular sequences in the virus life cycle. Forty Parvoviridae terminal repeats (TR) were publicly available in databases. The folding and specific DNA secondary structures, such as G4 and triplex, were systematically analyzed. A principal component analysis was carried out from the prediction data to determine variables signing parvovirus groups. A special focus will be put on adeno-associated virus (AAV) inverted terminal repeats (ITR), a member of the genus Dependoparvovirus used as vectors for gene therapy. This chapter highlights the diversity of the Parvoviridae telomeres regarding shape and secondary structures, providing information that could be relevant for virus-host interactions studies.

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“… Predicted structures of terminal repeat from described densoviruses (RNA-fold program) as in reference ( 50 ). We can see familiar structures like Y-shape or I-shape.…”

“…Densoviruses have a classical structure, two coding ORF cassettes and untranslated regions at the ends, with five out of nine having terminal repeats while others lack them. Not all known members of Densovirinae have terminal repetition at their genome ends ( 50 ). Our constructed phylogenetic tree was based on the conserved domain of NS1 even though the most described genera of Densovirinae clustered together, group previously classified as Ambidensovirus, and encompassing all the new -ambidensoviruses, were distributed through the tree with low bootstrap support.…”

“…Schemes of the genomes were generated using the Python library DNA Features Viewer v3.1.2 ( 49 ) and pyCirclize v0.5.0 ( https://github.com/moshi4/pyCirclize ), and other libraries were used to process data (Pandas, Numpy, Biopython). The terminal repeats were predicted by RNA-fold as specified in reference ( 50 ). The genomes of AmFLV and AmNV were polished using Pilon v1.24 ( 51 ).…”

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“…ITRs are also essential for replication, encapsulation and genome integration (Siegl and Tratschin, 1987;Zádori et al, 2001). Due to the presence of palindromic repeats, the most common structure found in the Densovirinae subfamily are J-shaped telomeres, but they can also be found in T-, I-, Y-, U-or simple hairpin-like structures (Laugel et al, 2022). However, the predicted structure of the ITRs for this new virus presented a unique trident-like shape.…”