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==Genome== Parvoviruses have linear, single-stranded DNA (ssDNA) genomes that are about 4–6 kilobases (kb) in length. The parvovirus genome typically contains two genes, termed the NS/rep gene and the VP/cap gene.<ref name=mietzsch >{{cite journal |vauthors=Mietzsch M, Pénzes JJ, Agbandje-McKenna M |date=20 April 2019 |title=Twenty-Five Years of Structural Parvovirology |journal= Viruses|volume=11 |issue=4 |pages=362 |doi=10.3390/v11040362 |pmc=6521121 |pmid=31010002|doi-access=free }}</ref> The NS gene encodes the non-structural (NS) protein NS1, which is the replication initiator protein, and the VP gene encodes the viral protein (VP) that the viral capsid is made of. NS1 contains an [[HUH-tag|HUH superfamily]] [[endonuclease]] domain near its [[N-terminus]], containing both site-specific binding activity and site-specific nicking activity, and a superfamily 3 (SF3) [[helicase]] domain toward the [[C-terminus]]. Most parvoviruses contain a transcriptional activation domain near the C-terminus that [[Downregulation and upregulation|upregulates]] transcription from viral [[Promoter (genetics)|promoters]] as well as alternate or overlapping [[open reading frame]]s that encode a small number of supporting proteins involved in different aspects of the viral life cycle.<ref name=cotmoreictv >{{cite journal |vauthors=Cotmore SF, Agbandje-McKenna M, Canuti M, Chiorini JA, Eis-Hubinger AM, Hughes J, Mietzsch M, Modha S, Ogliastro M, Pénzes JJ, Pintel DJ, Qiu J, Soderlund-Venermo M, Tattersall P, Tijssen P |date=March 2019 |title=ICTV Virus Taxonomy Profile: Parvoviridae |url=https://ictv.global/report/chapter/parvoviridae/parvoviridae |journal=J Gen Virol |volume=100 |issue=3 |pages=367–368 |doi=10.1099/jgv.0.001212 |pmc=6537627 |pmid=30672729 |access-date=24 January 2021}}</ref> The coding portion of the genome is flanked at each end by terminal sequences about 116–550 nucleotides (nt) in length that consist of imperfect palindromes folded into [[Stem-loop|hairpin loop]] structures. These hairpin loops contain most of the ''cis''-acting information required for DNA replication and packaging and act as hinges during replication to change the direction of replication. When the genome is converted to double-stranded forms, replication origin sites are created involving sequences in and adjacent to the hairpins.<ref name=cotmoreictv />{{sfn|Kerr|Cotmore|Bloom|2005|p=177}} Genomic DNA strands in mature virions may be [[Sense (molecular biology)|positive-sense or negative-sense]]. This varies from species to species as some have a preference for packaging strands of one polarity, others package varying proportions, and others package both sense strands at equal proportions. These preferences reflect the efficiency with which progeny strands are synthesized, which in turn reflects the efficiency of specific replication origin sites.<ref name=cotmoreictv /> The 3′-end (usually pronounced "three prime end") of a negative sense strand, and the 5′-end (usually pronounced "five prime end") of a positive sense strand, is called the left end, and the 5′-end of the negative sense strand, and the 3′-end of a positive sense strand, is called the right end.<ref name=cotmoreictv />{{sfn|Kerr|Cotmore|Bloom|2005|p=172}}<ref name=cotmore2013 >{{cite journal |vauthors=Cotmore SF, Tattersall P |date=1 February 2013 |title=Parvovirus diversity and DNA damage responses |journal=Cold Spring Harb Perspect Biol |volume=5 |issue=2 |pages=a012989 |doi=10.1101/cshperspect.a012989 |pmc=3552509 |pmid=23293137}}</ref>
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