1887

Journal of General Virology header logo

Volume 100, Issue 12

Genetic and phenotypic intrastrain variation in herpes simplex virus type 1 Glasgow strain 17 syn+-derived viruses Free

Abstract

The Glasgow s17 syn+ strain of herpes simplex virus 1 (HSV1) is arguably the best characterized strain and has provided the reference sequence for HSV1 genetic studies. Here we show that our original s17 syn+ stock was a mixed population from which we have isolated a minor variant that, unlike other strains in the laboratory, fails to be efficiently released from infected cells and spreads predominantly by direct cell-to-cell transmission. Analysis of other s17-derived viruses that had been isolated elsewhere revealed a number with the same release phenotype. Second-generation sequencing of 8 plaque-purified s17-derived viruses revealed sequences that vary by 50 single-nucleotide polymorphisms (SNPs), including approximately 10 coding SNPs. This compared to interstrain variations of around 800 SNPs in strain Sc16, of which a quarter were coding changes. Amongst the variations found within s17, we identified 13 variants of glycoprotein C within the original stock of virus that were predominantly a consequence of altered homopolymeric runs of C residues. Characterization of seven isolates coding for different forms of gC indicated that all were expressed, despite six of them lacking a transmembrane domain. While the release phenotype did not correlate directly with any of these identified gC variations, further demonstration that nine clinical isolates of HSV1 also fail to spread through extracellular release raises the possibility that propagation in tissue culture had altered the HSV1 s17 transmission phenotype. Hence, the s17 intrastrain variation identified here offers an excellent model for understanding both HSV1 transmission and tissue culture adaptation.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): cell-to-cell spread , glycoprotein C , herpes simplex virus and sequence diversity
Funding
This study was supported by the:
  • Worldwide Cancer Research (Award 15-0341)
    • Principle Award Recipient: Gill Elliott
© 2019 The Authors
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001343
2019-10-29
2024-04-26
Loading full text...

Full text loading...

/deliver/fulltext/jgv/100/12/1701.html?itemId=/content/journal/jgv/10.1099/jgv.0.001343&mimeType=html&fmt=ahah

References

  1. Wilson AC, Mohr I. A cultured affair: HSV latency and reactivation in neurons. Trends Microbiol 2012; 20:604–611 [View Article]
     [Google Scholar]
  2. Whitley RJ. Herpes simplex encephalitis: adolescents and adults. Antiviral Res 2006; 71:141–148 [View Article]
     [Google Scholar]
  3. Farooq AV, Shukla D. Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Surv Ophthalmol 2012; 57:448–462 [View Article]
     [Google Scholar]
  4. Tognarelli EI, Palomino TF, Corrales N, Bueno SM, Kalergis AM et al. Herpes simplex virus evasion of early host antiviral responses. Front Cell Infect Microbiol 2019; 9:127 [View Article]
     [Google Scholar]
  5. McGeoch DJ, Dalrymple MA, Davison AJ, Dolan A, Frame MC et al. The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1. J Gen Virol 1988; 69:1531–1574 [View Article]
     [Google Scholar]
  6. Macdonald SJ, Mostafa HH, Morrison LA, Davido DJ. Genome sequence of herpes simplex virus 1 strain KOS. J Virol 2012; 86:6371–6372 [View Article]
     [Google Scholar]
  7. Colgrove RC, Liu X, Griffiths A, Raja P, Deluca NA et al. History and genomic sequence analysis of the herpes simplex virus 1 KOS and KOS1.1 sub-strains. Virology 2016; 487:215–221 [View Article]
     [Google Scholar]
  8. Macdonald SJ, Mostafa HH, Morrison LA, Davido DJ. Genome sequence of herpes simplex virus 1 strain McKrae. J Virol 2012; 86:9540–9541 [View Article]
     [Google Scholar]
  9. Szpara ML, Parsons L, Enquist LW. Sequence variability in clinical and laboratory isolates of herpes simplex virus 1 reveals new mutations. J Virol 2010; 84:5303–5313 [View Article]
     [Google Scholar]
  10. Szpara ML, Gatherer D, Ochoa A, Greenbaum B, Dolan A et al. Evolution and diversity in human herpes simplex virus genomes. J Virol 2014; 88:1209–1227 [View Article]
     [Google Scholar]
  11. Pfaff F, Groth M, Sauerbrei A, Zell R. Genotyping of herpes simplex virus type 1 by whole-genome sequencing. J Gen Virol 2016; 97:2732–2741 [View Article]
     [Google Scholar]
  12. Rekabdar E, Tunbäck P, Liljeqvist JA, Lindh M, Bergström T. Dichotomy of glycoprotein G gene in herpes simplex virus type 1 isolates. J Clin Microbiol 2002; 40:3245–3251 [View Article]
     [Google Scholar]
  13. Liljeqvist JA, Svennerholm B, Bergström T. Herpes simplex virus type 2 glycoprotein G-negative clinical isolates are generated by single frameshift mutations. J Virol 1999; 73:9796–9802
     [Google Scholar]
  14. Wilkinson GWG, Davison AJ, Tomasec P, Fielding CA, Aicheler R et al. Human cytomegalovirus: taking the strain. Med Microbiol Immunol 2015; 204:273–284 [View Article]
     [Google Scholar]
  15. Brown SM, Ritchie DA, Subak-Sharpe JH. Genetic studies with herpes simplex virus type 1. The isolation of temperature-sensitive mutants, their arrangement into complementation groups and recombination analysis leading to a linkage map. J Gen Virol 1973; 18:329–346 [View Article]
     [Google Scholar]
  16. Parsons LR, Tafuri YR, Shreve JT, Bowen CD, Shipley MM et al. Rapid genome assembly and comparison decode intrastrain variation in human alphaherpesviruses. MBio 2015; 6:e02213-14 [View Article]
     [Google Scholar]
  17. Hill TJ, Field HJ, Blyth WA. Acute and recurrent infection with herpes simplex virus in the mouse: a model for studying latency and recurrent disease. J Gen Virol 1975; 28:341–353 [View Article]
     [Google Scholar]
  18. Elliott G, Hafezi W, Whiteley A, Bernard E. Deletion of the herpes simplex virus VP22-encoding gene (UL49) alters the expression, localization, and virion incorporation of ICP0. J Virol 2005; 79:9735–9745 [View Article]
     [Google Scholar]
  19. Coulter LJ, Moss HW, Lang J, McGeoch DJ. A mutant of herpes simplex virus type 1 in which the UL13 protein kinase gene is disrupted. J Gen Virol 1993; 74:387–395 [View Article]
     [Google Scholar]
  20. Fenwick ML, Everett RD. Inactivation of the shutoff gene (UL41) of herpes simplex virus types 1 and 2. J Gen Virol 1990; 71:2961–2967 [View Article]
     [Google Scholar]
  21. Everett RD, Boutell C, Orr A. Phenotype of a herpes simplex virus type 1 mutant that fails to express immediate-early regulatory protein ICP0. J Virol 2004; 78:1763–1774 [View Article]
     [Google Scholar]
  22. Smith KO. Relationship between the envelope and the infectivity of herpes simplex virus. Exp Biol Med 1964; 115:814–816 [View Article]
     [Google Scholar]
  23. Milne I, Bayer M, Cardle L, Shaw P, Stephen G et al. Tablet--next generation sequence assembly visualization. Bioinformatics 2010; 26:401–402 [View Article]
     [Google Scholar]
  24. Watson SJ, Welkers MRA, Depledge DP, Coulter E, Breuer JM et al. Viral population analysis and minority-variant detection using short read next-generation sequencing. Philos Trans R Soc Lond B Biol Sci 2013; 368:20120205 [View Article]
     [Google Scholar]
  25. Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 2009; 25:1754–1760 [View Article]
     [Google Scholar]
  26. Bellastella A, Amato G, Bizzaro A, Carella C, Criscuolo T et al. Light, blindness and endocrine secretions. J Endocrinol Invest 1999; 22:874–885 [View Article]
     [Google Scholar]
  27. Hillary W, Lin SH, Upton C. Base-By-Base version 2: single nucleotide-level analysis of whole viral genome alignments. Microb Inform Exp 2011; 1:2 [View Article]
     [Google Scholar]
  28. Sattentau Q. Avoiding the void: cell-to-cell spread of human viruses. Nat Rev Microbiol 2008; 6:815–826 [View Article]
     [Google Scholar]
  29. Weller TH, Witton HM. The etiologic agents of varicella and herpes zoster; serologic studies with the viruses as propagated in vitro . J Exp Med 1958; 108:869–890 [View Article]
     [Google Scholar]
  30. Biggs PM. The history and biology of Marek's disease virus. Curr Top Microbiol Immunol 2001; 255:1–24 [View Article]
     [Google Scholar]
  31. Dou D, Revol R, Östbye H, Wang H, Daniels R. Influenza A virus cell entry, replication, virion assembly and movement. Front Immunol 2018; 9:1581 [View Article]
     [Google Scholar]
  32. Jolly C, Kashefi K, Hollinshead M, Sattentau QJ. Hiv-1 cell to cell transfer across an Env-induced, actin-dependent synapse. J Exp Med 2004; 199:283–293 [View Article]
     [Google Scholar]
  33. Bowen CD, Paavilainen H, Renner DW, Palomäki J, Lehtinen J et al. Comparison of herpes simplex virus 1 strains circulating in Finland demonstrates the uncoupling of whole-genome relatedness and phenotypic outcomes of viral infection. J Virol 2019; 93: [View Article]
     [Google Scholar]
  34. Rastrojo A, López-Muñoz AD, Alcamí A. Genome sequence of herpes simplex virus 1 strain SC16. Genome Announc 2017; 5:e01392-16 [View Article]
     [Google Scholar]
  35. Stow ND, Stow EC. Isolation and characterization of a herpes simplex virus type 1 mutant containing a deletion within the gene encoding the immediate early polypeptide Vmw110. J Gen Virol 1986; 67:2571–2585 [View Article]
     [Google Scholar]
  36. Cunha CW, Taylor KE, Pritchard SM, Delboy MG, Komala Sari T et al. Widely used herpes simplex virus 1 ICP0 deletion mutant strain dl1403 and its derivative viruses do not express glycoprotein C due to a secondary mutation in the gC gene. PLoS One 2015; 10:e0131129 [View Article]
     [Google Scholar]
  37. Draper KG, Costa RH, Lee GT, Spear PG, Wagner EK. Molecular basis of the glycoprotein-C-negative phenotype of herpes simplex virus type 1 macroplaque strain. J Virol 1984; 51:578–585
     [Google Scholar]
  38. Sedlackova L, Perkins KD, Lengyel J, Strain AK, van Santen VL et al. Herpes simplex virus type 1 ICP27 regulates expression of a variant, secreted form of glycoprotein C by an intron retention mechanism. J Virol 2008; 82:7443–7455 [View Article]
     [Google Scholar]
  39. Kinchington PR, Remenick J, Ostrove JM, Straus SE, Ruyechan WT et al. Putative glycoprotein gene of varicella-zoster virus with variable copy numbers of a 42-base-pair repeat sequence has homology to herpes simplex virus glycoprotein C. J Virol 1986; 59:660–668
     [Google Scholar]
  40. Gaudreau A, Hill E, Balfour HH, Erice A, Boivin G. Phenotypic and genotypic characterization of acyclovir-resistant herpes simplex viruses from immunocompromised patients. J Infect Dis 1998; 178:297–303 [View Article]
     [Google Scholar]
  41. Kolakofsky D. Paramyxovirus RNA synthesis, mRNA editing, and genome hexamer phase: a review. Virology 2016; 498:94–98 [View Article]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.001343
Loading
Genetic and phenotypic intrastrain variation in herpes simplex virus type 1 Glasgow strain 17 syn+-derived viruses
J. Gen. Virol. 100, 1701 (2019); https://doi.org/10.1099/jgv.0.001343
/content/journal/jgv/10.1099/jgv.0.001343
/content/journal/jgv/10.1099/jgv.0.001343
Loading

Data & Media loading...

Most cited Most Cited RSS feed

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