Archives of Virology

, Volume 164, Issue 10, pp 2479–2491 | Cite as

The relationship of codon usage to the replication strategy of parvoviruses

  • Thanyaporn Sirihongthong
  • Kunlakanya Jitobaom
  • Supinya Phakaratsakul
  • Chompunuch Boonarkart
  • Ornpreya Suptawiwat
  • Prasert AuewarakulEmail author
Original Article


Codon usage is biased in most species, and the pattern of codon usage bias is specific to each species or group of closely related species. Although viruses use the host translational machinery for synthesis of their proteins, their codon usage patterns do not match those of their host. Viral codon usage is determined by a complex interplay of mutational bias, genome composition constraints, translational adaptation to the host, and host cellular innate defense. The codon usage of parvoviruses was previously shown not to be strongly biased and selective pressure was found to be a dominating factor driving codon usage. The family Parvoviridae includes the genus Dependoparvovirus, some of the members of which require a helper virus to complete their replication cycle, whereas the rest of the family can replicate without the need for helper viruses. Here, we show that difference in the replication strategy of these viruses may be an important factor determining viral codon usage. Hierarchical clustering and principal component analysis revealed that the codon usage pattern of adeno-associated viruses (AAVs) of the genus Dependoparvovirus is distinct from that of members of the other genera of vertebrate parvoviruses, and even from that of independent viruses of the genus Dependoparvovirus. Furthermore, the codon usage of human AAVs was found to be similar to that of some human adenoviruses in hierarchical clustering and principal component analysis. This suggests that the codon usage of AAVs is different from that of other parvoviruses because of their distinctive replication strategy and that their codon usage is probably driven by forces similar to those that shaped the codon usage pattern of their helper viruses.



This work was supported financially by Siriraj Graduate Scholarship and the Thailand Research Fund (Grant No. IRN60W0002).

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

Research involving human participants and/or animals

No part of this study was performed with human participants or animals.


  1. 1.
    Alazard-Dany N, Nicolas A, Ploquin A, Strasser R, Greco A, Epstein AL, Fraefel C, Salvetti A (2009) Definition of herpes simplex virus type 1 helper activities for adeno-associated virus early replication events. PLoS Pathog 5:e1000340CrossRefGoogle Scholar
  2. 2.
    Brown KE, Green SW, Young NS (1995) Goose parvovirus—an autonomous member of the dependovirus genus? Virology 210:283–291CrossRefGoogle Scholar
  3. 3.
    Bulmer M (1987) Coevolution of codon usage and transfer RNA abundance. Nature 325:728–730CrossRefGoogle Scholar
  4. 4.
    Comeron JM, Aguade M (1998) An evaluation of measures of synonymous codon usage bias. J Mol Evol 47:268–274CrossRefGoogle Scholar
  5. 5.
    Cotmore SF, Tattersall P (2013) Parvovirus diversity and DNA damage responses. Cold Spring Harb Perspect Biol 5:a012989CrossRefGoogle Scholar
  6. 6.
    Cotmore SF, Tattersall P (2014) Parvoviruses: small does not mean simple. Annu Rev Virol 1:517–537CrossRefGoogle Scholar
  7. 7.
    Das S, Paul S, Dutta C (2006) Synonymous codon usage in adenoviruses: influence of mutation, selection and protein hydropathy. Virus Res 117:227–236CrossRefGoogle Scholar
  8. 8.
    Duret L (2000) tRNA gene number and codon usage in the C. elegans genome are co-adapted for optimal translation of highly expressed genes. Trends Genet TIG 16:287–289CrossRefGoogle Scholar
  9. 9.
    Espinola EE, Barrios JC, Russomando G, Mirazo S, Arbiza J (2017) Computational analysis of a species D human adenovirus provides evidence of a novel virus. J Gen Virol 98:2810–2820CrossRefGoogle Scholar
  10. 10.
    Kailasan S, Agbandje-McKenna M, Parrish CR (2015) Parvovirus family conundrum: what makes a killer? Annu Rev Virol 2:425–450CrossRefGoogle Scholar
  11. 11.
    Lukashov VV, Goudsmit J (2001) Evolutionary relationships among parvoviruses: virus-host coevolution among autonomous primate parvoviruses and links between adeno-associated and avian parvoviruses. J Virol 75:2729–2740CrossRefGoogle Scholar
  12. 12.
    Luo Y, Qiu J (2013) Parvovirus infection-induced DNA damage response. Future Virol 8:245–257CrossRefGoogle Scholar
  13. 13.
    Ming XJY, Babiuk LA, Qian Y (2017) The host signaling pathways hijacked by oncogenic viruses. SM Vaccine Vaccin 3:1020Google Scholar
  14. 14.
    Nasrullah I, Butt AM, Tahir S, Idrees M, Tong Y (2015) Genomic analysis of codon usage shows influence of mutation pressure, natural selection, and host features on Marburg virus evolution. BMC Evol Biol 15:174CrossRefGoogle Scholar
  15. 15.
    Penzes JJ, Pham HT, Benko M, Tijssen P (2015) Novel parvoviruses in reptiles and genome sequence of a lizard parvovirus shed light on Dependoparvovirus genus evolution. J Gen Virol 96:2769–2779CrossRefGoogle Scholar
  16. 16.
    Puigbo P, Bravo IG, Garcia-Vallve S (2008) CAIcal: a combined set of tools to assess codon usage adaptation. Biol Direct 3:38CrossRefGoogle Scholar
  17. 17.
    Qian W, Yang JR, Pearson NM, Maclean C, Zhang J (2012) Balanced codon usage optimizes eukaryotic translational efficiency. PLoS Genet 8:e1002603CrossRefGoogle Scholar
  18. 18.
    Quax TE, Claassens NJ, Soll D, van der Oost J (2015) Codon bias as a means to fine-tune gene expression. Mol Cell 59:149–161CrossRefGoogle Scholar
  19. 19.
    Shi SL, Jiang YR, Liu YQ, Xia RX, Qin L (2013) Selective pressure dominates the synonymous codon usage in parvoviridae. Virus Genes 46:10–19CrossRefGoogle Scholar
  20. 20.
    Su MW, Lin HM, Yuan HS, Chu WC (2009) Categorizing host-dependent RNA viruses by principal component analysis of their codon usage preferences. J Comput Biol 16:1539–1547CrossRefGoogle Scholar
  21. 21.
    Sueoka N (1988) Directional mutation pressure and neutral molecular evolution. Proc Natl Acad Sci USA 85:2653–2657CrossRefGoogle Scholar
  22. 22.
    Wang H, Liu S, Zhang B, Wei W (2016) Analysis of synonymous codon usage bias of Zika virus and its adaption to the hosts. PLoS One 11:e0166260CrossRefGoogle Scholar
  23. 23.
    Wong EH, Smith DK, Rabadan R, Peiris M, Poon LL (2010) Codon usage bias and the evolution of influenza A viruses. Codon usage biases of influenza virus. BMC Evol Biol 10:253CrossRefGoogle Scholar
  24. 24.
    Wright F (1990) The ‘effective number of codons’ used in a gene. Gene 87:23–29CrossRefGoogle Scholar
  25. 25.
    Zhou JH, Zhang J, Sun DJ, Ma Q, Chen HT, Ma LN, Ding YZ, Liu YS (2013) The distribution of synonymous codon choice in the translation initiation region of dengue virus. PloS One 8:e77239CrossRefGoogle Scholar
  26. 26.
    Zou W, Wang Z, Xiong M, Chen AY, Xu P, Ganaie SS, Badawi Y, Kleiboeker S, Nishimune H, Ye SQ, Qiu J (2018) Human parvovirus B19 utilizes cellular DNA replication machinery for viral DNA replication. J Virol 92:e01881-17CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Microbiology, Faculty of Medicine Siriraj HospitalMahidol UniversityBangkokThailand
  2. 2.Faculty of Medicine and Public Health, HRH Princess Chulabhorn College of Medical ScienceChulabhorn Royal AcademyBangkokThailand

Personalised recommendations