1887

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Volume 75, Issue 12

ICP34.5 influences herpes simplex virus type 1 maturation and egress from infected cells Free

Abstract

We have previously demonstrated that efficient replication of mutant herpes simplex virus which fails to synthesize the polypeptide ICP34.5 is cell type and cell state dependent. ICP34.5 negative viruses do not grow in stationary state mouse embryo fibroblast 3T6 cells whereas the growth kinetics in BHK cells are indistinguishable from those of wild-type. We now demonstrate that this defect is not due to an inability of mutant virus to adsorb to 3T6 cells but rather to an inability to spread from the initially infected cells. Electron microscopic studies with wild-type HSV in both BHK and 3T6 cells revealed virus particles equally distributed between nucleus and cytoplasm, and additionally in the extracellular matrix. In BHK cells infected with the ICP34.5 negative mutant 1716, virus is likewise distributed between nucleus and cytoplasm but in 50 % of the infected cells there is marked delamination and swelling of the nuclear membrane. In addition there is evidence of a significant number of particles trapped between the nuclear lamellae. When 1716 is used to infect 3T6 cells, over 90% of the virus particles are confined to the nuclei and the number of infected cells remains constant between 24 and 48 h with no increase in the proportion of extracellular virus. Failure to express ICP34.5 appears therefore to result in a defect in virus maturation and egress from the nuclei of infected cells. Egress of HSV from the nuclei to the extracellular space is thought to occur via two pathways. We postulate that lack of expression of ICP34.5 results in one of these pathways being blocked. In BHK cells this leads to overloading of the alternative pathway with a buildup of particles in the nuclear lamellae and associated endoplasmic reticulum. In stationary state 3T6 cells, it appears that there is no functional alternative pathway. We conclude that ICP34.5 exerts an effect on HSV maturation by controlling the passage of virus through infected cells.

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© The Journal of General Virology 1994
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1994-12-01
2024-04-18
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References

  1. 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. Journal of Virology 58:843–850
     [Google Scholar]
  2. Brown S. M., Ritchie D. A., Subak-Sharpe J. H. 1973; Genetic studies with herpes simplex virus type 1. The isolation of temperature sensitive mutants, their arrangements into complementation groups and recombination analysis leading to a linkage map. Journal of General Virology 18:329–346
     [Google Scholar]
  3. Brown S. M., Harland J., Maclean A. R., Podlech J., Clements J. B. 1994; Cell type and cell state determine differential in vitro growth of non-neurovirulent ICP34.5 negative herpes simplex virus. Journal of General Virology 75:2367–2377
     [Google Scholar]
  4. 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]
  5. Chou J., Kern E. R., Whitley R. J., Roizman B. 1990; Mapping of herpes simplex virus 1 neurovirulence to 34.5, a gene non-essential for growth in culture. Science 250:1262–1265
     [Google Scholar]
  6. Dargan D. 1986; The structure and assembly of herpes viruses. In Electron Microscopy of Proteins 5 Viral Structure pp. 359–437 Harris J. R., Horne R. W. Edited by London: Academic Press;
     [Google Scholar]
  7. Dolan A., Mckie E., Maclean A. R., Mcgeoch D. J. 1992; Status of the ICP34.5 gene in herpes simplex virus type 1 strain 17. Journal of General Virology 73:971–973
     [Google Scholar]
  8. Mackay E. M., Mcvey G., Marsden H. S., Brown S. M., Maclean A. R. 1993; The herpes simplex virus type 1 open reading frame RL1 encodes a polypeptide of apparent Mr 37K equivalent to ICP34.5 of herpes simplex virus type 1 strain F. Journal of General Virology 74:2493–2497
     [Google Scholar]
  9. Mckie A. E., Hope R. S., Brown S. M., Maclean A. R. 1994; Characterization of the herpes simplex virus type 1 strain 17+ neurovirulence gene RL1 and its expression in a bacterial system. Journal of General Virology 75:733–741
     [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. Rixon F. J. 1993; Structure and assembly of herpes viruses. Seminars in Virology 4 pp. 135–144 London: Academic Press;
     [Google Scholar]
  12. Robertson L. M., Maclean A. R., Brown S. M. 1992; Peripheral replication and latency reactivation kinetics of the non-neurovirulent herpes simplex virus type 1 variant 1716. Journal of General Virology 73:967–970
     [Google Scholar]
  13. 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]
  14. Taha M. Y., Clements G. B., Brown S. M. 1989b; The herpes simplex virus type 2 strain HG52 variant JH2604 has a 1488 bp deletion which eliminates neuro virulence in mice. Journal of General Virology 70:3073–3078
     [Google Scholar]
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ICP34.5 influences herpes simplex virus type 1 maturation and egress from infected cells in vitro
J. Gen. Virol. 75, 3679 (1994); https://doi.org/10.1099/0022-1317-75-12-3679
/content/journal/jgv/10.1099/0022-1317-75-12-3679
/content/journal/jgv/10.1099/0022-1317-75-12-3679
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