1887

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Volume 72, Issue 9

The R neurovirulence locus in herpes simplex virus type 2 strain HG52 plays no role in latency Free

Abstract

We have demonstrated that the variant JH2604 of the herpes simplex virus type 2 (HSV-2) strain HG52 is completely avirulent in BALB/c mice following intracranial inoculation, with an LD of > 10 p.f.u./mouse compared to the wild-type LD of < 10 p.f.u./mouse. In JH2604, a 1.5 kbp deletion extends from the DR1/Ub junction of the ‘a’ sequence to 511 bp upstream of the 5′ end of IE1 in both long repeats. We have since constructed a second variant (2701) in which only 850 bp are removed from the R. This deletion lies entirely within the sequences deleted in JH2604 and leaves intact most of a short 189 bp open reading frame (ORF) highly conserved between HSV-1 and HSV-2. Like JH2604, 2701 shows wild-type growth characteristics and is neither host range-nor temperature-restricted. This was most noteworthy in the case of mouse 3T6 cells. 2701 has an LD of 5×10 p.f.u./mouse on intracranial inoculation, a value intermediate between those of HG52 and JH2604. In assays for intracranial replication, JH2604 exhibits no detectable growth with a rapid decline in virus titre, 2701 shows limited growth over the first 24 to 36 h post-inoculation before the titre again declines and HG52 grows rapidly, reaching a high titre until the mice die. Taken together these results suggest that a region of the genome upstream of IE1 encodes a gene product essential for HSV replication in neurons of the central nervous system. It is highly likely that the conserved ORF is in an important region of a polypeptide essential for neurovirulence, although the upstream sequences present in 2701 but absent from JH2604 must also play a role. Although JH2604 and 2701 are avirulent, they both establish latent infection in the dorsal root ganglia of BALB/c mice and reactivate in a manner indistinguishable from HG52. This suggests a distinct separation of the factors involved in neurovirulence and the establishment of/reactivation from latency.

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  • Accepted:
  • Published Online:
© Journal of General Virology 1991
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1991-09-01
2024-04-24
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References

  1. Ace C. I., McKee T. A., Ryan J. M., Cameron J. M., Preston C. M. 1989; Construction and characterization of a herpes simplex type 1 virus mutant unable to transinduce immediate-early gene expression. Journal of Virology 63:2260–2269
     [Google Scholar]
  2. Ackermann M., Chou J., Sarmiento M., Lerner R. A., Roizman B. 1986; Identification by antibody to a synthetic peptide of a protein specified by a diploid gene located in the terminal repeats of the L component of herpes simplex virus genome. Journal of Virology 58:843–850
     [Google Scholar]
  3. Cameron J. M., McDougall I., Marsden H. S., Preston V. G., Ryan D. M., Subak-Sharpe J. H. 1988; Ribonucleotide reductase encoded by herpes simplex virus is a determinant of the pathogenicity of the virus in mice and a valid antiviral target. Journal of General Virology 69:2607–2612
     [Google Scholar]
  4. Chou J., Roizman B. 1986; The terminal ‘a’ sequence of the herpes simplex virus genome contains the promoter of a gene located in the repeat sequences of the L component. Journal of Virology 57:629–637
     [Google Scholar]
  5. Chou J., Roizman B. 1990; The herpes simplex virus 1 gene for ICP34-5 which maps in inverted repeats is conserved in several limited passage isolates but not in strain 17 syn+ . Journal of Virology 64:1014–1020
     [Google Scholar]
  6. Chou J., Kern E. K., Whitley R. J., Roizman B. 1990; Mapping of herpes simplex virus 1 neurovirulence to gamma 1 34.5, a gene non-essential for growth in culture. Science 250:1262–1266
     [Google Scholar]
  7. Efstathiou S., Kemp S., Darby G., Minson A. C. 1989; The role of herpes simplex virus type 1 thymidine kinase in pathogenesis. Journal of General Virology 70:869–879
     [Google Scholar]
  8. Harland J., Brown S. M. 1985; Isolation and characterization of deletion mutants of herpes simplex virus type 2 (strain HG52). Journal of General Virology 66:1305–1321
     [Google Scholar]
  9. Leib D. A., Bogard C. L., Kosz-Vnenchak M., Hicks K. A., Coen D. M., Knipe D. M., Schaffer P. A. 1989; A deletion mutant of the latency associated transcript of herpes simplex virus type 1 reactivates from the latent state with reduced frequency. Journal of Virology 63:2893–2900
     [Google Scholar]
  10. MacLean A. R., Fareed M. U., Robertson L., Harland J., Brown S. M. 1991; Herpes simplex virus type 1 deletion variants 1714 and 1716 pinpoint neurovirulence-related sequences in Glasgow strain 17+ between immediate early gene 1 and the ‘a’ sequence. Journal of General Virology 72:631–639
     [Google Scholar]
  11. Spivack J. G., Fraser N. W. 1987; Detection of herpes simplex virus type 1 transcripts during latent infection in mice. Journal of Virology 61:3841–3847
     [Google Scholar]
  12. Steiner I., Spivack J. G., Lirette R. P., Brown S. M., MacLean A. R., Subak-Sharpe J. H., Fraser N. W. 1989; Herpes simplex virus type 1 latency-associated transcripts are evidently not essential for latent infection. EMBO Journal 8:505–511
     [Google Scholar]
  13. Steiner I., Spivack J. G., Deshmane S. L., Ace C. I., Preston C. M., Fraser N. W. 1990; A herpes simplex virus type 1 mutant containing a non-transinducing Vmw65 protein establishes latent infection in vivo in the absence of viral replication and reactivates efficiently from explanted trigeminal ganglia. Journal of Virology 64:1630–1638
     [Google Scholar]
  14. Taha M. Y., Brown S. M., Clements G. B. 1988; Neurovirulence of individual plaque stocks of herpes simplex virus type 2 strain HG52. Archives of Virology 103:15–25
     [Google Scholar]
  15. Taha M. Y., Clements G. B., Brown S. M. 1989a; A variant of herpes simplex virus type 2 strain HG52 with a 1.5 kb deletion in RL between 0 to 0.02 and 0.81 to 0.83 map units is non-neurovirulent for mice. Journal of General Virology 70:705–716
     [Google Scholar]
  16. Taha M. Y., Clements G. B., Brown S. M. 1989b; The herpes simplex virus type 2 (HG52) variant JH2604 has a 1488 bp deletion which eliminates neurovirulence in mice. Journal of General Virology 70:3073–3078
     [Google Scholar]
  17. Taha M. Y., Brown S. M., Clements G. B., Graham D. I. 1990; The JH2604 deletion variant of herpes simplex virus type 2 (HG52) fails to produce necrotizing encephalitis following intracranial inoculation of mice. Journal of General Virology 71:1597–1601
     [Google Scholar]
  18. Thomson R. L., Wagner E. K., Stevens J. G. 1983; Physical location of a herpes simplex virus type 1 function(s) specifically involved with a 10 million fold increase in HSV neurovirulence. Virology 131:180–192
     [Google Scholar]
  19. Thomson R. L., Rogers S. K., Zerhusen M. A. 1989; Herpes simplex virus neurovirulence and productive infection of neural cells is associated with a function which maps between 0.82–0.832 map units on the HSV genome. Virology 172:435–450
     [Google Scholar]
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The RL neurovirulence locus in herpes simplex virus type 2 strain HG52 plays no role in latency
J. Gen. Virol. 72, 2305 (1991); https://doi.org/10.1099/0022-1317-72-9-2305
/content/journal/jgv/10.1099/0022-1317-72-9-2305
/content/journal/jgv/10.1099/0022-1317-72-9-2305
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