**1. Introduction**

Many linear DNA viruses possess terminal repeats (TRs) known to be critical for viral genome stability and propagation [1]. A parallel can be drawn with human chromosome telomeres that are composed of GC-rich repeat sequences of 5–10 nucleotides. In cells, telomeres are critical to maintain the linear structure of the chromosomes. They can adopt specific secondary structures, such as G-quadruplexes (G4), providing structural characteristics for protein binding and genomic stability. In addition, Cellular telomeres play a role in transcription regulation, chromatin compaction, subcellular localization, and chromosome segregation.

Similarly, *Parvoviridae* TRs have been demonstrated to be essential to several steps of the virus cycle. They vary in shape and size from approximatively 100 to 550

nucleotides [2]. Due to the presence of palindromic repeats, TRs can fold into T-, I-, J-, Y-, U- shape or simple hairpin-like structures. Up to now, the global shape has been named without any consensus, for example, Y-shape also being called "rabbit ears."

Viral genomes in some genera (*Ambi*- and *Itera-densovirus*; *Ave*-, *Dependo*-and *Erythro-parvovirus*) are homotelomeric meaning that both termini are similar but inverted, whereas, in other genera (*Brevi*- and *Hepan*-*densovirus*; *Amdo*-, *Boca*- and *Proto*-*parvovirus*), the 5<sup>0</sup> and 3<sup>0</sup> ends of the linear genome differ and therefore are called heterotelomeric. The strand polarity packed in viral capsids may be related to the left and right TRs dissimilarity. Indeed, most of the heterotelomeric parvoviruses encapsidate only one strand polarity, mainly negative. This preference may be due to inefficient nicking during replication or incomplete packaging signal at one TR [2]; for example, the minute virus of mice (MVM), a virus of the subfamily *Parvovirinae* and genus *Protoparvovirus*, harbors a Y-shape left end and a longer U-shape structure on its right end. After replication and ori resolution, the single-stranded DNA of minus polarity is preferentially displaced from the left TR and encapsidated. For parvovirus with both polarities, the proportion can range from 1 to 50% and may be influenced by the host cell in which the virus is produced [3].

Parvoviral TRs are involved in many steps of the virus life cycle. They contain most of the *cis*-acting information required for genome replication and encapsidation, including tetranucleotide repeats that serve as binding sites for NS1 (Rep) oligomer, a resolution site necessary for the completion of the DNA strand copy, and a packaging signal. Recognized as DNA double-strand breaks (DSB) in the host cell, TR can trigger a DNA damage response (DDR), leading to the circularization and concatemerization of the viral genomes either by non-homologous end-joining (NHEJ) or homologous recombination (HR) [4]. Finally, transcription regulation elements are contained in the genome ends. For example, the MVM TRs contain both symmetric and asymmetric binding sites for transcription factors that modulate expression from the adjacent P4 promoter [5] and the Acheta Domestica Densovirus TRs contain a TATA box used for transcription initiation of NS gene on one side and VP on the other side [6].

The TRs secondary structures, motifs composition, and their role in the virus-cell cycle have been under-examined. In this study, DNA secondary structures of the *Parvoviridae* TRs, including non-canonical secondary structures, have been predicted. We have shown a high diversity of parvovirus telomeres characteristics even within a genus. This chapter may provide significant knowledge for *Parvoviridae* classification and interaction with host cells*.*
