A Herpes Simplex Virus Type 1 Mutant with a Deletion in the Polypeptide-coding Sequences of the ICP4 Gene

Schröder, Claus H.; DeZazzo, J D; Knopf, Karl-Werner; Kaerner, Hans Christian; Levine, Myron

doi:10.1099/0022-1317-66-7-1589

Cited by 13 publications

(9 citation statements)

References 23 publications

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“…Therefore, the first 90 amino acids of ICP4 are not required for viral growth. The viability of a previously described mutant containing a 96 amino acid deletion near the amino terminus of ICP4 is consistent with this conclusion (45).…”

Section: Discussionsupporting

confidence: 85%

Activities of herpes simplex virus type 1 (HSV-1) ICP4 genes specifying nonsense peptides

1987

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Synthetic oligonucleotide linkers containing translational termination codons in all possible reading frames were inserted at various positions in the cloned gene encoding the herpes simplex virus type 1 (HSV-1) immediate-early regulatory protein, ICP4. It was determined that the amino-terminal 60 percent of the ICP4 gene was sufficient for trans-induction of a thymidine kinase promoter-CAT chimera (pTKCAT) and negative regulation of an ICP4 promoter-CAT chimera (pIE3CAT); however, it was relatively inefficient in complementing an ICP4 deletion mutant. The amino-terminal ninety amino acids do not appear to be required for infectivity as reflected by the replication competence of a mutant virus containing a linker insertion at amino acid 12. The size of the ICP4 molecule expressed from the mutant virus was consistent with translational restart at the next methionine codon corresponding to amino acid 90 of the deduced ICP4 amino acid sequence.

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Section: Discussionsupporting

confidence: 85%

Activities of herpes simplex virus type 1 (HSV-1) ICP4 genes specifying nonsense peptides

1987

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“…We view this as indicating that these localities of the gene show particular plasticity in mutation to a high G+C contentthat is, they may encode polypeptide whose composition is not critical to IE175 function. This is supported by the work of Schrbder et al (48), who described an HSV-1 mutant with an internal, in-frame deletion in the IE175 gene. This removed codons 209 to 236, but the resulting virus was still viable.…”

Section: Ddvwggrggrsppqsrgmentioning

confidence: 63%

Complete DNA sequence of the short repeat region in the genome of herpes simplex virus type 1

McGeoch¹,

Dolan²,

Donald³

et al. 1986

Nucl Acids Res

321

249

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We report the complete DNA sequence of the short repeat region in the genome of herpes simplex virus type 1, as 6633 base pairs of composition 79.5% G+C. This contains immediate early gene 3, encoding the IE175 protein, an important transcriptional activator of later virus genes. The IE175 coding region was identified as a 3894 base sequence of 81.5% G+C DNA. The base composition of this gene is thus the most extreme yet determined, and the IE175 predicted amino acid composition is correspondingly biased, most notably with an alanine content of 20.9%. Functionally important regions of the IE175 polypeptide were tentatively identified by comparison with the sequence of the homologous protein from varicella-zoster virus and from locations of ts mutations, and were correlated with properties of the amino acid sequence. Aspects of the evolution of such an extreme composition DNA sequence were discussed.

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“…An ICP4 mutant viral strain lacking the region "a" which is proficient for viral growth has been described previously (11,12), resulting from translational restart at residue 90 due to the insertion of a translation termination codon at amino acid residue 12. A spontaneous deletion mutant proficient for growth, which lacks residues 209 through 236 specifying region "b", has also been described previously (46). n208 molecule.…”

Section: Discussionmentioning

confidence: 91%

“…7 and 8) are indicated below the positions of insertions. Sequences previously shown to be important for phosphorylation and nuclear localization (12), as well as two regions found to be nonessential for viral growth (11,12,46), are also indicated. An ICP4 mutant viral strain lacking the region "a" which is proficient for viral growth has been described previously (11,12), resulting from translational restart at residue 90 due to the insertion of a translation termination codon at amino acid residue 12.…”

Section: Discussionmentioning

confidence: 99%

Separation of primary structural components conferring autoregulation, transactivation, and DNA-binding properties to the herpes simplex virus transcriptional regulatory protein ICP4

Shepard

Imbalzano

DeLuca

1989

J Virol

104

109

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A truncated ICP4 peptide which contains the amino-terminal 774 amino acids of the 1,298-amino-acid polypeptide is proficient for DNA binding, autoregulation, and transactivation of some viral genes (N. A. DeLuca and P. A. Schaffer, J. Virol. 62:732-743, 1988) and hence exhibits many of the properties characteristic of intact ICP4. To define the primary sequence important for the activities inherent in the amino-terminal half of the ICP4 molecule, insertional and deletion mutagenesis of the sequences encoding these residues were conducted. The DNA-binding activity of the molecule as assayed by the association with a consensus binding site was sensitive to insertional mutagenesis in two closely linked regions of the molecule. One region between amino acids 445 and 487 is critical for DNA binding and may contain a helix-turn-helix motif. The second region between amino acids 263 and 338 reduces the binding activity to a consensus binding site. When analyzed in the viral background, the DNA-binding activity of a peptide containing an insertion at amino acid 338 to a consensus binding site was reduced while the association with an alternative sequence was eliminated, suggesting a possible mechanism by which ICP4 may recognize a broader range of sequence elements. Mutations which eliminated DNA binding also eliminated or reduced both transactivation and autoregulation, supporting the requirement for DNA binding for these activities. Peptides that retained the deduced DNA-binding domain but lacked amino acids 143 through 210 retained the ability to associate with the consensus site and autoregulatory activity but were deficient for transactivation, demonstrating that the structural requirements for transactivation are greater than those required for autoregulation.

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A Herpes Simplex Virus Type 1 Mutant with a Deletion in the Polypeptide-coding Sequences of the ICP4 Gene

Cited by 13 publications

References 23 publications

Activities of herpes simplex virus type 1 (HSV-1) ICP4 genes specifying nonsense peptides

Activities of herpes simplex virus type 1 (HSV-1) ICP4 genes specifying nonsense peptides

Complete DNA sequence of the short repeat region in the genome of herpes simplex virus type 1

Separation of primary structural components conferring autoregulation, transactivation, and DNA-binding properties to the herpes simplex virus transcriptional regulatory protein ICP4

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