Establishment of latency in vitro by the herpes simplex virus type 1 mutant in 1814

Harris, R; Preston, Chris M.

doi:10.1099/0022-1317-72-4-907

Cited by 62 publications

(81 citation statements)

References 33 publications

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“…From this, the other VP16-induced IE gene products may be evolutionary consequences of viral replication in the face of robust host defensive responses during reactivation and therefore have no obligate roles in the initial stages of reactivation from latency. There is accumulating genetic data to support this view (2,8,24).…”

Section: Vol 76 2002 Microarray Analysis Of Hsv-1 Vp16 Activation Mmentioning

confidence: 94%

General and Specific Alterations in Programming of Global Viral Gene Expression during Infection by VP16 Activation-Deficient Mutants of Herpes Simplex Virus Type 1

Yang

Devi-Rao

Ghazal³

et al. 2002

J Virol

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During productive infection by herpes simplex virus 1 (HSV-1), viral gene expression occurs in a temporally regulated cascade in which transcription of the viral immediate-early (IE) genes is strongly stimulated by the virion protein VP16. We have employed an oligonucleotide microarray to examine the effect of VP16 mutations on the overall pattern of viral gene expression following infection of HeLa cells. This microarray detects essentially all HSV-1 transcripts with relative and absolute levels correlating well with known kinetics of expression. This analysis revealed that deletion of the VP16 activation domain sharply reduced overall viral gene expression; moreover, the pattern of this reduced expression varied greatly from the pattern of a wild-type (wt) infection. However, when this mutant virus was delivered at a high multiplicity of infection or in the presence of the cellular stress inducer hexamethylene bisacetamide, expression was largely restored to the wt levels and pattern. Infection with virions that deliver wt VP16 protein at the start of infection but synthesize only truncated VP16 resulted in a normal kinetic cascade. This suggests that newly synthesized VP16 does not play a significant role in the expression of later classes of transcripts. The VP16 activation domain comprises two subregions. Deletion of the C-terminal subregion resulted in minimal changes in the level and profile of gene expression compared to a normal (wt) cascade. In contrast, deletion of the N-terminal subregion reduced the overall expression levels and skewed the relative levels of IE transcripts but did not significantly alter the kinetic pattern of early and late transcript expression. We conclude that the general activation of IE gene transcription by VP16, but not the specific ratios of IE transcripts, is necessary for the subsequent ordered expression of viral genes. Moreover, this report establishes the feasibility of microarray analysis for globally assessing viral gene expression programs as a function of the conditions of infection.During productive infection of mammalian cells by herpes simplex virus type 1 (HSV-1), transcription of the viral genes occurs in a coordinated cascade (11, 28; reviewed in references 34 and 37). The five viral immediate-early (IE) genes are transcribed rapidly upon viral entry and uncoating. Synthesis of the IE proteins peaks at approximately 2 to 4 h postinfection (hpi), but they continue to accumulate throughout the infection. The IE proteins stimulate the expression of the early (E) and late (L) genes and also have autoregulatory functions.The virion protein VP16 activates transcription of the IE genes through specific sequence elements in the IE promoters (reviewed in reference 19). VP16 interacts with the viral DNA template by associating with the cellular proteins Oct-1 and HCF-1 at promoter elements containing the sequence TAAT-GARAT (where R represents purine) (reviewed in reference 9). Activation by VP16 is also exerted through DNA sequences bound by the cellular protein GABP ...

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Section: Vol 76 2002 Microarray Analysis Of Hsv-1 Vp16 Activation Mmentioning

confidence: 94%

General and Specific Alterations in Programming of Global Viral Gene Expression during Infection by VP16 Activation-Deficient Mutants of Herpes Simplex Virus Type 1

Yang

Devi-Rao

Ghazal³

et al. 2002

J Virol

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“…Production of functional IE110 has been shown to be important in reactivation of HSV both in vivo (Leib et al, 1989) and in an in vitro model of latency (Harris & Preston, 1991). Thus, detection of IE110 promoter-driven lacZ expression would be predicted to provide a sensitive marker for virus reactivation.…”

Section: The Assessment Of Ie110 Promoter Activity During Reactivatiomentioning

confidence: 99%

An analysis of herpes simplex virus gene expression during latency establishment and reactivation.

Lachmann

Sadarangani

Atkinson

et al. 1999

Journal of General Virology

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In order to facilitate an analysis of the pattern of herpes simplex virus gene expression during latency establishment and reactivation, recombinant viruses containing the lacZ reporter gene under control of either the immediate early 110 (IE110) promoter or the latency-associated promoter have been constructed. Histochemical staining of ganglia taken from mice infected with these viruses allows for the rapid identification and quantification of sensory neurones in which these two promoters are active. Using the mouse ear model, this study demonstrates that, during the establishment of latency in vivo, IE110 promoter activity is only detectable in ganglia which provide innervation to the site of virus inoculation. Latency, however, is efficiently established not only in these ganglia, but also in adjacent ganglia whose neurones do not innervate the ear, and in which there was no evidence of IE110 expression during the acute phase of infection. This implies that replication-competent virus can efficiently establish latency in the absence of detectable IE110 expression. In addition, it has been possible to investigate viral gene expression in neurones following ganglionic explant culture by monitoring IE110 promoter-driven lacZ expression within reactivating neurones. This study shows that virus can be reactivated from all latently infected ganglia, but that reactivation appears to be more efficient from ganglia which provide innervation to the site of infection. The implications of these results for the mechanisms involved in latency establishment and reactivation are discussed.

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“…As a consequence of reduced IE transcription, in1814 is unable to initiate productive infection efficiently and thus, at low m.o.i., only a small proportion (0.1 1%, depending ~n the cell type) of virus-cell interactions result in virus replication (Ace et al, 1989;Daksis & Preston, 1992). The vast majority of infected cells harbour the in1814 genome in a stable quiescent state that has been termed ~in vitro latency' (Harris & Preston, 1991). By 1 day after infection, in1814 genomes become insensitive to activation by Vmw65 or hexamethylene bisacetamide (HMBA), even though these agents effectively complement the defect in virus replication if applied at the time of infection (Ace et al, 1989;Harris & Preston, 1991 ;McFarlane et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Quiescent viral genomes in human fibroblasts after infection with herpes simplex virus type 1 Vmw65 mutants

Jamieson¹,

Robinson²,

Daksis³

et al. 1995

Journal of General Virology

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Establishment of latency in vitro by the herpes simplex virus type 1 mutant in 1814

Cited by 62 publications

References 33 publications

General and Specific Alterations in Programming of Global Viral Gene Expression during Infection by VP16 Activation-Deficient Mutants of Herpes Simplex Virus Type 1

General and Specific Alterations in Programming of Global Viral Gene Expression during Infection by VP16 Activation-Deficient Mutants of Herpes Simplex Virus Type 1

An analysis of herpes simplex virus gene expression during latency establishment and reactivation.

Quiescent viral genomes in human fibroblasts after infection with herpes simplex virus type 1 Vmw65 mutants

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