Activation of second-messenger pathways reactivates latent herpes simplex virus in neuronal cultures

Smith, Roderic L.; Pizer, Lewis I.; Johnson, Eugene M.; Wilcox, Christine L.

doi:10.1016/0042-6822(92)90760-m

Cited by 66 publications

(70 citation statements)

References 44 publications

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“…We next tested to see whether latent ZEBOV infection, like other latent infections, such as herpesvirus or human immunodeficiency virus (HIV) (30)(31)(32), could be induced to replicate to higher titers through physiological treatments. Typically, RAW ZEBOVpi cells produced low levels of viral expression, as determined by GFP expression (Fig.…”

Section: Resultsmentioning

confidence: 99%

Stimulation of Ebola virus production from persistent infection through activation of the Ras/MAPK pathway

Strong

Wong²,

Jones³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Human infections with Ebola virus (EBOV) result in a deadly viral disease known as Ebola hemorrhagic fever. Up to 90% of infected patients die, and there is no available treatment or vaccine. The sporadic human outbreaks are believed to result when EBOV ''jumps'' from an infected animal to a person and is subsequently transmitted between persons by direct contact with infected blood or body fluids. This study was undertaken to investigate the mechanism by which EBOV can persistently infect and then escape from model cell and animal reservoir systems. We report a model system in which infection of mouse and bat cell lines with EBOV leads to persistence, which can be broken with low levels of lipopolysaccharide or phorbol-12-myristate-13-acetate (PMA). This reactivation depends on the Ras/MAPK pathway through inhibition of RNA-dependent protein kinase and eukaryotic initiation factor 2␣ phosphorylation and occurs at the level of protein synthesis. EBOV also can be evoked from mice 7 days after infection by PMA treatment, indicating that a similar mechanism occurs in vivo. Our findings suggest that EBOV may persist in nature through subclinical infection of a reservoir species, such as bats, and that appropriate physiological stimulation may result in increased replication and transmission to new hosts. Identification of a presumptive mechanism responsible for EBOV emergence from its reservoir underscores the ''hit-and-run'' nature of the initiation of human and/or nonhuman primate EBOV outbreaks and may provide insight into possible countermeasures to interfere with transmission.

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Section: Resultsmentioning

confidence: 99%

Stimulation of Ebola virus production from persistent infection through activation of the Ras/MAPK pathway

Strong

Wong²,

Jones³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…This model suggests that NGF is required for the maintenance of neuronal latency since its removal results in viral reactivation. Later studies have shown that the mechanism of NGF dependent latency involves binding of NGF to the NGF receptor (TrkA) and the stimulation of second messenger pathways (Smith et al, 1992). It has also been found that interruption of RNA transcription or protein synthesis in these latently-infected cells results in viral reactivation with similar kinetics to NGF withdrawal.…”

Section: A Viral Vector For Gene Therapymentioning

confidence: 97%

The roles of herpes simplex virus in neuroscience

Turner¹,

Jenkins²

1997

J Neurovirol

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Herpes simplex virus (HSV) has been a focus of research in many laboratories during the last 30 ± 35 years, with the majority centered on the virus' replication, molecular biology and pathogenesis. Recently, HSV has begun to receive considerable attention in the field of neuroscience, where scientists have begun to use the virus as a tool or model for several areas of investigation. These areas include the construction and development of HSV-based vectors for gene therapy and the use of HSV as a neuronal tracer, as a model for demyelinating disease and to study interactions between the nervous, immune and endocrine systems. The goal of this paper is to review these different roles for HSV in the broad field of neuroscience.

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“…For co-cultivations, fibroblasts were plated with green turtle keratinocytes (20 000-40 000 cells per well). When cells reached 75 % confluence (4-5 days), cultures were incubated with 1 mM sodium butyrate for 1, 3 and 5 days (Yu et al, 1999), 20 ng phorbol 12-myristate 13-acetate (TPA) ml 21 for 1, 3 and 5 days (Yu et al, 1999), 50 mM forskolin for 4 days (Smith et al, 1992), 1 mM isobutylmetaxanthine for 4 days (Smith et al, 1992), 10 ng tumour necrosis factor alpha (TNF-a) ml 21 for 4 days (Kitano et al, 1993), 5 mM trichostatin A for 18 h (Countryman et al, 2008), 20 mg iododeoxyuridine (IUDR) ml 21 for 48 h (Nazerian, 1975), 20 mg IUDR ml 21 for 24 h plus 10 nM dexamethasone for 24-72 h (Paran et al, 1973), 10 mM valproic acid for 18 h (Countryman et al, 2008), 10 mM norepinephrine or 1 nM epinephrine for 24 h (Chang et al, 2005), 1 % DMSO for 4 days (Tanaka et al, 1985), 5 mM hexamethylenebisacetamide for 4 days (Bernstein & Kappes, 1988), 10 mM 5-azacytidine for 4 days (Chen et al, 2001) and 1 mM dexamethasone for 24-72 h (Paran et al, 1973). All chemicals were from Sigma, except for dexamethasone and epinephrine, which were from Phoenix Pharmaceutical and MP Biomedicals, respectively.…”

mentioning

confidence: 99%

In vitro biology of fibropapilloma-associated turtle herpesvirus and host cells in Hawaiian green turtles (Chelonia mydas)

Work

Dagenais

Balazs

et al. 2009

Journal of General Virology

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Fibropapillomatosis (FP) of green turtles has a global distribution and causes debilitating tumours of the skin and internal organs in several species of marine turtles. FP is associated with a presently non-cultivable alphaherpesvirus Chelonid fibropapilloma-associated herpesvirus (CFPHV). Our aims were to employ quantitative PCR targeted to pol DNA of CFPHV to determine (i) if DNA sequesters by tumour size and/or cell type, (ii) whether subculturing of cells is a viable strategy for isolating CFPHV and (iii) whether CFPHV can be induced to a lytic growth cycle in vitro using chemical modulators of replication (CMRs), temperature variation or co-cultivation. Additional objectives included determining whether non-tumour and tumour cells behave differently in vitro and confirming the phenotype of cultured cells using cell-type-specific antigens. CFPHV pol DNA was preferentially concentrated in dermal fibroblasts of skin tumours and the amount of viral DNA per cell was independent of tumour size. Copy number of CFPHV pol DNA per cell rapidly decreased with cell doubling of tumour-derived fibroblasts in culture. Attempts to induce viral replication in known CFPHV-DNA-positive cells using temperature or CMR failed. No significant differences were seen in in vitro morphology or growth characteristics of fibroblasts from tumour cells and paired normal skin, nor from CFPHV pol-DNA-positive intestinal tumour cells. Tumour cells were confirmed as fibroblasts or keratinocytes by positive staining with antivimentin and anti-pancytokeratin antibodies, respectively. CFPHV continues to be refractory to in vitro cultivation.

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Activation of second-messenger pathways reactivates latent herpes simplex virus in neuronal cultures

Cited by 66 publications

References 44 publications

Stimulation of Ebola virus production from persistent infection through activation of the Ras/MAPK pathway

Stimulation of Ebola virus production from persistent infection through activation of the Ras/MAPK pathway

The roles of herpes simplex virus in neuroscience

In vitro biology of fibropapilloma-associated turtle herpesvirus and host cells in Hawaiian green turtles (Chelonia mydas)

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