Herpes simplex virus latency and reactivation in isolated rat sensory neurons

Wigdahl, Brian; Ziegler, Richard J.; Sneve, Mary; Rapp, Fred

doi:10.1016/0042-6822(83)90380-x

Cited by 46 publications

(42 citation statements)

References 29 publications

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“…The systems with the most obvious relevance to latency in animals and humans utilize foetal neurons from rats or primates (Wigdahl et al, 1983(Wigdahl et al, , 1984bWilcox & Johnson, 1987Wilcox et al, 1990). Infection of cultured rat foetal neurons with HSV is non-productive provided an inhibitor of DNA synthesis is present for a few days after infection and nerve growth factor (NGF) is included in the culture medium.…”

Section: Introductionmentioning

confidence: 99%

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

Harris

Preston²

1991

Journal of General Virology

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The herpes simplex virus type 1 (HSV-1) mutant in1814 possesses an insertion mutation that abolishes trans-activation of immediate early (IE) transcription by the virion protein Vmw65. Interactions between in 1814 and the host cell were examined by use of an in vitro latency system which relies on infection of human foetal lung (HFL) cells at 42 °C to prevent lytic growth of virus. Mutant in 1814 was retained in HFL cells after infection at low m.o.i, and incubation at 42 °C, and was reactivated by superinfection of monolayers with viruses that express the HSV-1 IE protein Vmw110. Moreover, latency was established by in1814 in an analogous manner at 37 °C. The low cytotoxicity of in1814 enabled an investigation of latency after infection at high m.o.i. (five particles per cell) to be undertaken. At 42 °C, or at 37 oC in the presence of an inhibitor of DNA synthesis, in1814 DNA was maintained at low abundance (one to eight copies per infected cell) in a non-linear configuration. The absence of trans-activation by Vmw65 therefore predisposes HSV to latency, as opposed to lytic growth, in HFL cells, resulting in the retention of the genome in a form resembling that found in vivo.

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Section: Introductionmentioning

confidence: 99%

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

Harris

Preston²

1991

Journal of General Virology

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“…Some of these systems use immortalized cells, derived from either human B cells or fibroblast cultures (Thiele et al, 1989;Russell & Preston, 1986), or defective virus (Geller & Breakfield, 1988). Another system, using primary cultures of dissected dorsal root ganglia, has many properties of the in vivo system including restricted transcription of the HSV genome and impaired reactivation of thymidine kinasenegative virus (Wigdahl et al, 1982;Wilcox & Johnson, 1988;Wilcox et al, 1990Wilcox et al, , 1992. However, preparation of dissected dorsal root ganglia is inconvenient.…”

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confidence: 99%

Long term herpes simplex virus type 1 infection of nerve growth factor-treated PC12 cells

Block

Barney

Masonis

et al. 1994

Journal of General Virology

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The behaviour of herpes simplex virus type 1 (HSV-I) strain 17 in tissue cultures of PC12 cells treated with nerve growth factor (NGF) was studied. PC12 cells respond to NGF by ceasing to proliferate and extending long neurites. After differentiation with NGF, cultures were infected with HSV-1 and maintained in the presence of the hormone for several weeks. These longterm infected cultures were tested for HSV DNA, transcripts and the ability to produce virus, before and after NGF removal. Before NGF removal, the cultures were characterized by little or no virus production and the presence of HSV-1 DNA in a predominantly endless form. In situ analysis of long-term infected cultures revealed latency-associated transcript expression in only a portion of the cells. However, as shown by an infectious centre assay, virus was present in almost all cells in the population. Moreover, removal of NGF from long-term cultures resulted in the appearance of significantly increased amounts of virus in the media. The degree to which this system resembles HSV latency in vivo is discussed.

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“…In general, these rely on the use of inhibitors to prevent viral replication and cell destruction but permit the earliest steps of the gene expression program to proceed. Reactivation of quiescence can be achieved in a number of ways, including heat shock, elevation of cAMP levels, removal of nerve growth factor, and addition of TSA, although only a small proportion of cells produce virus (2,11,12,46,66,69,75,76). Treatment of cultured ganglia isolated from latently infected mice by heat shock or addition of dexamethasone, but not agents that increase cAMP levels, stimulated reactivation (32).…”

Section: Discussionmentioning

confidence: 99%

Induction of Cellular Stress Overcomes the Requirement of Herpes Simplex Virus Type 1 for Immediate-Early Protein ICP0 and Reactivates Expression from Quiescent Viral Genomes

Preston

Nicholl

2008

J Virol

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Herpes simplex virus type 1 (HSV-1) mutants impaired in the activities of the structural protein VP16 and the immediate-early (IE) proteins ICP0 and ICP4 establish a quiescent infection in human fibroblasts, with most cells retaining an inactive, repressed viral genome for sustained periods in culture. To date, the quiescent state has been considered stable, since it has been reversed only by provision of herpesviral proteins, such as ICP0, not by alteration of the cell physiological state. We report that the interaction of HSV-1 with human fibroblasts can be altered significantly by transient treatment of cultures with sodium arsenite, an inducer of heat shock and oxidative stress, or gramicidin D, a toxin that selectively permeabilizes cell membranes, prior to infection. These regimens stimulated gene expression from IE-deficient HSV-1 mutants in a promoter sequence-independent manner and also overcame the replication defect of ICP0-null mutants. Reactivation of gene expression from quiescent HSV-1 genomes and the resumption of virus replication were observed following addition of arsenite or gramicidin D to cultures. Both agents induced reorganization of nuclear domain 10 structures, the sites of quiescent genomes, but appeared to do so through different mechanisms. The results demonstrate that the physiological state of the cell is important in determining the outcome of infection with IE-deficient HSV-1 and show novel methods for reactivating quiescent HSV-1 in fibroblasts with a high efficiency.Transcription of the herpes simplex virus type 1 (HSV-1) genome at early stages of infection is controlled by the activities of three viral proteins, VP16, ICP4, and ICP0. VP16 is a virion component that stimulates immediate-early (IE) transcription through interaction with the cellular proteins Oct-1 and HCF-1 (51, 77). ICP4 is an IE protein that is essential for early and late gene expression, acting on basal cellular transcription factors (10,64,80). The IE protein ICP0 exerts a general stimulatory effect on HSV-1 transcription and is important for initiation of the viral gene expression program (17,19,31,61,68).The VP16 and ICP4 proteins can be viewed as conventional transcription activators since they interact with cellular factors that localize to promoter regions of the viral genome. In contrast, the effects of ICP0 are not promoter specific or even restricted to the HSV-1 genome, since the protein stimulates gene expression from a variety of plasmids and viruses (3,18,30,31,48,52). One of the most striking features of ICP0 is its effect on cellular intranuclear structures known as promyelocytic leukemia (PML) bodies or nuclear domain 10 (ND10). Early in infection, ICP0 localizes to ND10 and directs the disruption of these bodies (21,22). Protein components of ND10, including the PML protein itself, are targeted for degradation due to a ubiquitin E3 ligase activity that requires the RING domain of ICP0 (6,21,25). HSV-1 mutants that lack the ICP0 coding region exhibit a multiplicity-and cell type-dependent def...

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Herpes simplex virus latency and reactivation in isolated rat sensory neurons

Cited by 46 publications

References 29 publications

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

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

Long term herpes simplex virus type 1 infection of nerve growth factor-treated PC12 cells

Induction of Cellular Stress Overcomes the Requirement of Herpes Simplex Virus Type 1 for Immediate-Early Protein ICP0 and Reactivates Expression from Quiescent Viral Genomes

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