1887

Abstract

Congenital infection by human cytomegalovirus (HCMV) is a major cause of birth defects and developmental abnormalities. Since guinea pig cytomegalovirus (GPCMV) crosses the placenta and causes infection , GPCMV models are useful for studies of the mechanisms of transplacental transmission. During our characterization of a genomic locus required for GPCMV dissemination in animals, we found that the nucleotide sequence in and around the nearby immediate–early genes in our lineage of GPCMV strain 22122 [designated GPCMV (ATCC-P5)] showed clear differences from that reported previously for the same strain [designated GPCMV (UMN)] passaged extensively . Since passaging of HCMV is known to result in genetic alterations, especially in the UL128–UL131A locus, and loss of growth ability in particular cell types, in this study we determined the complete genome sequence of GPCMV (ATCC-P5), which grows efficiently in animals. A total of 359 differences were identified between the genome sequences of GPCMV (UMN) and GPCMV (ATCC-P5), and these resulted in structural differences in 29 protein-encoding regions. In addition, some genes predicted from our analysis but not from GPCMV (UMN) are well conserved among cytomegaloviruses. An additional 18 passages of GPCMV (ATCC-P5) generated no further marked alterations in these genes or in the locus corresponding to the HCMV UL128–UL131A. Our analyses indicate that the published sequence of GPCMV (UMN) contains a substantial number of sequencing errors and, possibly, some mutations resulting from a long history of passaging . Our re-evaluation of the genetic content of GPCMV will provide a solid foundation for future studies.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.027789-0
2011-05-01
2019-12-11
Loading full text...

Full text loading...

/deliver/fulltext/jgv/92/5/1005.html?itemId=/content/journal/jgv/10.1099/vir.0.027789-0&mimeType=html&fmt=ahah

References

  1. Akter P. , Cunningham C. , McSharry B. P. , Dolan A. , Addison C. , Dargan D. J. , Hassan-Walker A. F. , Emery V. C. , Griffiths P. D. et al. ( 2003; ). Two novel spliced genes in human cytomegalovirus. . J Gen Virol 84:, 1117–1122. [CrossRef] [PubMed]
    [Google Scholar]
  2. Bates M. , Monze M. , Bima H. , Kapambwe M. , Kasolo F. C. , Gompels U. A. . CIGNIS study group ( 2008; ). High human cytomegalovirus loads and diverse linked variable genotypes in both HIV-1 infected and exposed, but uninfected, children in Africa. . Virology 382:, 28–36. [CrossRef] [PubMed]
    [Google Scholar]
  3. Besemer J. , Lomsadze A. , Borodovsky M. . ( 2001; ). GeneMarkS: a self-training method for prediction of gene starts in microbial genomes. Implications for finding sequence motifs in regulatory regions. . Nucleic Acids Res 29:, 2607–2618. [CrossRef] [PubMed]
    [Google Scholar]
  4. Bradley A. J. , Kovács I. J. , Gatherer D. , Dargan D. J. , Alkharsah K. R. , Chan P. K. , Carman W. F. , Dedicoat M. , Emery V. C. et al. ( 2008; ). Genotypic analysis of two hypervariable human cytomegalovirus genes. . J Med Virol 80:, 1615–1623. [CrossRef] [PubMed]
    [Google Scholar]
  5. Bradley A. J. , Lurain N. S. , Ghazal P. , Trivedi U. , Cunningham C. , Baluchova K. , Gatherer D. , Wilkinson G. W. , Dargan D. J. , Davison A. J. . ( 2009; ). High-throughput sequence analysis of variants of human cytomegalovirus strains Towne and AD169. . J Gen Virol 90:, 2375–2380. [CrossRef] [PubMed]
    [Google Scholar]
  6. Brocchieri L. , Kledal T. N. , Karlin S. , Mocarski E. S. . ( 2005; ). Predicting coding potential from genome sequence: application to betaherpesviruses infecting rats and mice. . J Virol 79:, 7570–7596. [CrossRef] [PubMed]
    [Google Scholar]
  7. Bühler B. , Keil G. M. , Weiland F. , Koszinowski U. H. . ( 1990; ). Characterization of the murine cytomegalovirus early transcription unit e1 that is induced by immediate-early proteins. . J Virol 64:, 1907–1919.[PubMed]
    [Google Scholar]
  8. Cha T. A. , Tom E. , Kemble G. W. , Duke G. M. , Mocarski E. S. , Spaete R. R. . ( 1996; ). Human cytomegalovirus clinical isolates carry at least 19 genes not found in laboratory strains. . J Virol 70:, 78–83.[PubMed]
    [Google Scholar]
  9. Cheng T. P. , Valentine M. C. , Gao J. , Pingel J. T. , Yokoyama W. M. . ( 2010; ). Stability of murine cytomegalovirus genome after in vitro and in vivo passage. . J Virol 84:, 2623–2628. [CrossRef] [PubMed]
    [Google Scholar]
  10. Ciocco-Schmitt G. M. , Karabekian Z. , Godfrey E. W. , Stenberg R. M. , Campbell A. E. , Kerry J. A. . ( 2002; ). Identification and characterization of novel murine cytomegalovirus M112-113 (e1) gene products. . Virology 294:, 199–208. [CrossRef] [PubMed]
    [Google Scholar]
  11. Cui X. , McGregor A. , Schleiss M. R. , McVoy M. A. . ( 2008; ). Cloning the complete guinea pig cytomegalovirus genome as an infectious bacterial artificial chromosome with excisable origin of replication. . J Virol Methods 149:, 231–239. [CrossRef] [PubMed]
    [Google Scholar]
  12. Cunningham C. , Gatherer D. , Hilfrich B. , Baluchova K. , Dargan D. J. , Thomson M. , Griffiths P. D. , Wilkinson G. W. , Schulz T. F. , Davison A. J. . ( 2010; ). Sequences of complete human cytomegalovirus genomes from infected cell cultures and clinical specimens. . J Gen Virol 91:, 605–615. [CrossRef] [PubMed]
    [Google Scholar]
  13. Dargan D. J. , Douglas E. , Cunningham C. , Jamieson F. , Stanton R. J. , Baluchova K. , McSharry B. P. , Tomasec P. , Emery V. C. et al. ( 2010; ). Sequential mutations associated with adaptation of human cytomegalovirus to growth in cell culture. . J Gen Virol 91:, 1535–1546. [CrossRef] [PubMed]
    [Google Scholar]
  14. Davison A. J. , Dolan A. , Akter P. , Addison C. , Dargan D. J. , Alcendor D. J. , McGeoch D. J. , Hayward G. S. . ( 2003; ). The human cytomegalovirus genome revisited: comparison with the chimpanzee cytomegalovirus genome. . J Gen Virol 84:, 17–28. [CrossRef] [PubMed]
    [Google Scholar]
  15. Dolan A. , Cunningham C. , Hector R. D. , Hassan-Walker A. F. , Lee L. , Addison C. , Dargan D. J. , McGeoch D. J. , Gatherer D. et al. ( 2004; ). Genetic content of wild-type human cytomegalovirus. . J Gen Virol 85:, 1301–1312. [CrossRef] [PubMed]
    [Google Scholar]
  16. Dominguez G. , Dambaugh T. R. , Stamey F. R. , Dewhurst S. , Inoue N. , Pellett P. E. . ( 1999; ). Human herpesvirus 6B genome sequence: coding content and comparison with human herpesvirus 6A. . J Virol 73:, 8040–8052.[PubMed]
    [Google Scholar]
  17. Hahn G. , Revello M. G. , Patrone M. , Percivalle E. , Campanini G. , Sarasini A. , Wagner M. , Gallina A. , Milanesi G. et al. ( 2004; ). Human cytomegalovirus UL131-128 genes are indispensable for virus growth in endothelial cells and virus transfer to leukocytes. . J Virol 78:, 10023–10033. [CrossRef] [PubMed]
    [Google Scholar]
  18. Hassan-Walker A. F. , Okwuadi S. , Lee L. , Griffiths P. D. , Emery V. C. . ( 2004; ). Sequence variability of the alpha-chemokine UL146 from clinical strains of human cytomegalovirus. . J Med Virol 74:, 573–579. [CrossRef] [PubMed]
    [Google Scholar]
  19. Hirt B. . ( 1967; ). Selective extraction of polyoma DNA from infected mouse cell cultures. . J Mol Biol 26:, 365–369. [CrossRef] [PubMed]
    [Google Scholar]
  20. Igarashi K. , Fawl R. , Roller R. J. , Roizman B. . ( 1993; ). Construction and properties of a recombinant herpes simplex virus 1 lacking both S-component origins of DNA synthesis. . J Virol 67:, 2123–2132.[PubMed]
    [Google Scholar]
  21. Katano H. , Sato Y. , Tsutsui Y. , Sata T. , Maeda A. , Nozawa N. , Inoue N. , Nomura Y. , Kurata T. . ( 2007; ). Pathogenesis of cytomegalovirus-associated labyrinthitis in a guinea pig model. . Microbes Infect 9:, 183–191. [CrossRef] [PubMed]
    [Google Scholar]
  22. Kern E. R. . ( 2006; ). Pivotal role of animal models in the development of new therapies for cytomegalovirus infections. . Antiviral Res 71:, 164–171. [CrossRef] [PubMed]
    [Google Scholar]
  23. Koyano S. , Inoue N. , Nagamori T. , Yan H. , Asanuma H. , Yagyu K. , Osaki M. , Seiwa C. , Fujieda K. . ( 2009; ). Dried umbilical cords in the retrospective diagnosis of congenital cytomegalovirus infection as a cause of developmental delays. . Clin Infect Dis 48:, e93–e95. [CrossRef] [PubMed]
    [Google Scholar]
  24. Lai L. , Britt W. J. . ( 2003; ). The interaction between the major capsid protein and the smallest capsid protein of human cytomegalovirus is dependent on two linear sequences in the smallest capsid protein. . J Virol 77:, 2730–2735. [CrossRef] [PubMed]
    [Google Scholar]
  25. Lilja A. E. , Shenk T. . ( 2008; ). Efficient replication of rhesus cytomegalovirus variants in multiple rhesus and human cell types. . Proc Natl Acad Sci U S A 105:, 19950–19955. [CrossRef] [PubMed]
    [Google Scholar]
  26. Lurain N. S. , Fox A. M. , Lichy H. M. , Bhorade S. M. , Ware C. F. , Huang D. D. , Kwan S. P. , Garrity E. R. , Chou S. . ( 2006; ). Analysis of the human cytomegalovirus genomic region from UL146 through UL147A reveals sequence hypervariability, genotypic stability, and overlapping transcripts. . Virol J 3:, 4. [CrossRef] [PubMed]
    [Google Scholar]
  27. Mattick C. , Dewin D. , Polley S. , Sevilla-Reyes E. , Pignatelli S. , Rawlinson W. , Wilkinson G. , Dal Monte P. , Gompels U. A. . ( 2004; ). Linkage of human cytomegalovirus glycoprotein gO variant groups identified from worldwide clinical isolates with gN genotypes, implications for disease associations and evidence for N-terminal sites of positive selection. . Virology 318:, 582–597. [CrossRef] [PubMed]
    [Google Scholar]
  28. Murphy E. , Yu D. , Grimwood J. , Schmutz J. , Dickson M. , Jarvis M. A. , Hahn G. , Nelson J. A. , Myers R. M. , Shenk T. E. . ( 2003; ). Coding potential of laboratory and clinical strains of human cytomegalovirus. . Proc Natl Acad Sci U S A 100:, 14976–14981. [CrossRef] [PubMed]
    [Google Scholar]
  29. Nozawa N. , Yamamoto Y. , Fukui Y. , Katano H. , Tsutsui Y. , Sato Y. , Yamada S. , Inami Y. , Nakamura K. et al. ( 2008; ). Identification of a 1.6 kb genome locus of guinea pig cytomegalovirus required for efficient viral growth in animals but not in cell culture. . Virology 379:, 45–54. [CrossRef] [PubMed]
    [Google Scholar]
  30. Ogawa H. , Suzutani T. , Baba Y. , Koyano S. , Nozawa N. , Ishibashi K. , Fujieda K. , Inoue N. , Omori K. . ( 2007; ). Etiology of severe sensorineural hearing loss in children: independent impact of congenital cytomegalovirus infection and GJB2 mutations. . J Infect Dis 195:, 782–788. [CrossRef] [PubMed]
    [Google Scholar]
  31. Pass R. F. . ( 2001; ). Cytomegalovirus. . In Fields Virology, pp. 2675–2705. Edited by Knipe D. M. , Howley P. M. . . Philadelphia:: Lippincott Williams & Wilkins;.
    [Google Scholar]
  32. Rivailler P. , Kaur A. , Johnson R. P. , Wang F. . ( 2006; ). Genomic sequence of rhesus cytomegalovirus 180.92: insights into the coding potential of rhesus cytomegalovirus. . J Virol 80:, 4179–4182. [CrossRef] [PubMed]
    [Google Scholar]
  33. Ryckman B. J. , Rainish B. L. , Chase M. C. , Borton J. A. , Nelson J. A. , Jarvis M. A. , Johnson D. C. . ( 2008; ). Characterization of the human cytomegalovirus gH/gL/UL128-131 complex that mediates entry into epithelial and endothelial cells. . J Virol 82:, 60–70. [CrossRef] [PubMed]
    [Google Scholar]
  34. Schleiss M. R. . ( 2006; ). Nonprimate models of congenital cytomegalovirus (CMV) infection: gaining insight into pathogenesis and prevention of disease in newborns. . ILAR J 47:, 65–72.[PubMed] [CrossRef]
    [Google Scholar]
  35. Schleiss M. R. , McGregor A. , Choi K. Y. , Date S. V. , Cui X. , McVoy M. A. . ( 2008; ). Analysis of the nucleotide sequence of the guinea pig cytomegalovirus (GPCMV) genome. . Virol J 5:, 139. [CrossRef] [PubMed]
    [Google Scholar]
  36. Stanton R. , Westmoreland D. , Fox J. D. , Davison A. J. , Wilkinson G. W. . ( 2005; ). Stability of human cytomegalovirus genotypes in persistently infected renal transplant recipients. . J Med Virol 75:, 42–46. [CrossRef] [PubMed]
    [Google Scholar]
  37. Stanton R. J. , Baluchova K. , Dargan D. J. , Cunningham C. , Sheehy O. , Seirafian S. , McSharry B. P. , Neale M. L. , Davies J. A. et al. ( 2010; ). Reconstruction of the complete human cytomegalovirus genome in a BAC reveals RL13 to be a potent inhibitor of replication. . J Clin Invest 120:, 3191–3208. [CrossRef] [PubMed]
    [Google Scholar]
  38. Wang D. , Shenk T. . ( 2005; a). Human cytomegalovirus UL131 open reading frame is required for epithelial cell tropism. . J Virol 79:, 10330–10338. [CrossRef] [PubMed]
    [Google Scholar]
  39. Wang D. , Shenk T. . ( 2005; b). Human cytomegalovirus virion protein complex required for epithelial and endothelial cell tropism. . Proc Natl Acad Sci U S A 102:, 18153–18158. [CrossRef] [PubMed]
    [Google Scholar]
  40. Wood L. J. , Baxter M. K. , Plafker S. M. , Gibson W. . ( 1997; ). Human cytomegalovirus capsid assembly protein precursor (pUL80.5) interacts with itself and with the major capsid protein (pUL86) through two different domains. . J Virol 71:, 179–190.[PubMed]
    [Google Scholar]
  41. Wright D. A. , Spector D. H. . ( 1989; ). Posttranscriptional regulation of a class of human cytomegalovirus phosphoproteins encoded by an early transcription unit. . J Virol 63:, 3117–3127.[PubMed]
    [Google Scholar]
  42. Yamada S. , Nozawa N. , Katano H. , Fukui Y. , Tsuda M. , Tsutsui Y. , Kurane I. , Inoue N. . ( 2009; ). Characterization of the guinea pig cytomegalovirus genome locus that encodes homologs of human cytomegalovirus major immediate-early genes, UL128, and UL130. . Virology 391:, 99–106. [CrossRef] [PubMed]
    [Google Scholar]
  43. Yan H. , Koyano S. , Inami Y. , Yamamoto Y. , Suzutani T. , Mizuguchi M. , Ushijima H. , Kurane I. , Inoue N. . ( 2008; ). Genetic linkage among human cytomegalovirus glycoprotein N (gN) and gO genes, with evidence for recombination from congenitally and postnatally infected Japanese infants. . J Gen Virol 89:, 2275–2279. [CrossRef] [PubMed]
    [Google Scholar]
  44. Yu X. , Shah S. , Atanasov I. , Lo P. , Liu F. , Britt W. J. , Zhou Z. H. . ( 2005; ). Three-dimensional localization of the smallest capsid protein in the human cytomegalovirus capsid. . J Virol 79:, 1327–1332. [CrossRef] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.027789-0
Loading
/content/journal/jgv/10.1099/vir.0.027789-0
Loading

Data & Media loading...

Supplements

vol. , part 5, pp. 1005 –1020

Differences in nucleotide sequences between GPCMV (ATCC-P5) and GPCMV (UMN).

[ PDF file] (66 KB)

 



PDF

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error