Differential Effect of Murine Alpha/Beta Interferon Transgenes on Antagonization of Herpes Simplex Virus Type 1 Replication

Härle, Peter; Cull, Vanessa S.; Agbaga, Martin-Paul; Silverman, Robert H.; Williams, Bryan R.G.; James, Cassandra M.; Carr, Daniel J.J.

doi:10.1128/jvi.76.13.6558-6567.2002

Cited by 61 publications

(58 citation statements)

References 78 publications

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“…Results were calculated as DC T , the difference between the gene of interest and the b-actin gene mean thresholds, and expressed as expression levels relative to b-actin. 29 …”

Section: F-means Clustering Analysis Of Gene Expression Dynamicsmentioning

confidence: 99%

5α-Androstane-3α,17β-diol activates pathway that resembles the epidermal growth factor responsive pathways in stimulating human prostate cancer LNCaP cell proliferation

Zimmerman

Dozmorov

Nunlist

et al. 2004

Prostate Cancer Prostatic Dis

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5a-Androstane-3a,17b-diol (3a-diol) is considered to have no androgenic effects in androgen target organs unless it is oxidized to 5a-dihydrotestosterone (5a-DHT). We used microarray and bioinformatics to identify and compare 3a-diol and 5a-DHT responsive gene in human prostate LNCaP cells. Through a procedure called 'hypervariable determination', a similar set of 30 responsive genes involving signal transduction, transcription regulation, and cell proliferation were selected in 5a-DHT-, 3a-diol-, and epidermal growth factor (EGF)-treated samples. F-means cluster and networking procedures showed that the responsive pattern of these genes was more closely related between 3a-diol and EGF than between 5a-DHT and 3a-diol treatments. We conclude that 3a-diol is capable of stimulating prostate cell proliferation by eliciting EGF-like pathway in conjunction with androgen receptor pathway.

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“…Results were calculated as DC T , the difference between the gene of interest and the b-actin gene mean thresholds, and expressed as expression levels relative to b-actin. 29 …”

Section: F-means Clustering Analysis Of Gene Expression Dynamicsmentioning

confidence: 99%

5α-Androstane-3α,17β-diol activates pathway that resembles the epidermal growth factor responsive pathways in stimulating human prostate cancer LNCaP cell proliferation

Zimmerman

Dozmorov

Nunlist

et al. 2004

Prostate Cancer Prostatic Dis

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“…In DNA-vaccination studies with different IFN-a subtypes against murine cytomegalovirus (MCMV) infection, it was shown that vaccination with IFN-a1, IFN-a4 and IFN-a9 as adjuvants resulted in decreased viral loads after virus challenge in the muscle only, whereas vaccination with IFN-a6 inhibited MCMV replication in all the organs investigated. Two IFN-a subtypes (IFN-a2 and IFN-a5) were not able to reduce viral loads in these experiments (Cull et al, 2002). In contrast to MCMV infection, DNA-vaccination studies against influenza virus infection identified IFN-a5 and IFN-a6 to be the most efficient subtypes in reducing viral titres (James et al, 2007).…”

Section: Ifn-a Subtypesmentioning

confidence: 99%

“…In vitro studies demonstrated that IFN-a1, IFN-a4, IFN-a5, IFN-a6 and IFN-a9 mediate anti-viral activity against herpes simplex virus (Harle et al, 2002), whereas IFN-a11 and IFN-a4 were the best candidates in blocking the replication of mengovirus (van Pesch et al, 2004). In vivo, it was shown that during Friend retrovirus (FV) infection of mice, therapeutic treatment with IFN-a1, IFN-a4, IFN-a9 and IFN-a11 reduced the viral loads significantly, whereas IFN-a2, IFN-a5 and IFN-a6 could not inhibit viral replication (Gerlach et al, 2009;Gibbert et al, 2012).…”

Section: Ifn-a Subtypesmentioning

confidence: 99%

IFN‐α subtypes: distinct biological activities in anti‐viral therapy

Gibbert

Schlaak

Yang

et al. 2013

British J Pharmacology

144

138

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During most viral infections, the immediate host response is characterized by an induction of type I IFN. These cytokines have various biological activities, including anti‐viral, anti‐proliferative and immunomodulatory effects. After induction, they bind to their IFN‐α/β receptor, which leads to downstream signalling resulting in the expression of numerous different IFN‐stimulated genes. These genes encode anti‐viral proteins that directly inhibit viral replication as well as modulate immune function. Thus, the induction of type I IFN is a very powerful tool for the host to fight virus infections. Many viruses evade this response by various strategies like the direct suppression of IFN induction or inhibition of the IFN signalling pathway. Therefore, the therapeutic application of exogenous type I IFN or molecules that induce strong IFN responses should be of great potential for future immunotherapies against viral infections. Type I IFN is currently used as a treatment in chronic hepatitis B and C virus infection, but as yet is not widely utilized for other viral infections. One reason for this restricted clinical use is that type I IFN belongs to a multigene family that includes 13 different IFN‐α subtypes and IFN‐β, whose individual anti‐viral and immunomodulatory properties have so far not been investigated in detail to improve IFN therapy against viral infections in humans. In this review, we summarize the recent achievements in defining the distinct biological functions of type I IFN subtypes in cell culture and in animal models of viral infection as well as their clinical usage in chronic hepatitis virus infections.

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“…Mouse studies have shown that IFN−α1 and IFN−β were both effective in preventing mucosal HSV-1 infection, and that IFN−α2, −α4, −α5, −α6 and −α9 were ineffective [78][79][80]. Furthermore, IFN−β was found to be superior to IFN−α6 in preventing ocular HSV-1 infection in mice, via upregulation of ISG transcripts, 2-5OAS in trigeminal ganglia and increased phosphorylation of STAT1 [81].…”

Section: Ifns and Hsvsmentioning

confidence: 97%

“…Also, ICP27 induces the secretion of a type I IFN antagonist that inhibits STAT1 phosphorylation and nuclear localization [90]. However, IFN−β, more so than IFN−α, has been reported to reduce levels of ICP27 transcription as well as thymidine kinase and glycoprotein B, as determined by real-time PCR [78].…”

Section: Ifns and Hsvsmentioning

confidence: 99%

Interferons as Biomarkers and Effectors: Lessons Learned from Animal Models

2012

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Interferons (IFNs) comprise type I, II and III families with multiple subtypes. Via transcription of IFNstimulated genes (ISGs), IFNs can exert multiple biological effects on the cell. In infectious and chronic inflammatory diseases, the IFNs and their ISG sets can be potentially utilized as biomarkers of disease outcome. Animal models allow investigations into disease pathogenesis and gene knockout models have proved cause and effect relationships of molecules related to the IFN response. Sets of IFN subtypes and their ISG products provide immunological signature patterns for different viral and other diseases. In this article, we give an overview of IFNs in several virus infection models and autoimmune diseases of medical relevance. Lessons learned from animal models inform us of IFN system parameters as indicators of disease outcome and whether clinical research is warranted. Moreover, validated IFN biomarkers for prognosis enhance our understanding of therapeutic and vaccine development.

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Differential Effect of Murine Alpha/Beta Interferon Transgenes on Antagonization of Herpes Simplex Virus Type 1 Replication

Cited by 61 publications

References 78 publications

5α-Androstane-3α,17β-diol activates pathway that resembles the epidermal growth factor responsive pathways in stimulating human prostate cancer LNCaP cell proliferation

5α-Androstane-3α,17β-diol activates pathway that resembles the epidermal growth factor responsive pathways in stimulating human prostate cancer LNCaP cell proliferation

IFN‐α subtypes: distinct biological activities in anti‐viral therapy

Interferons as Biomarkers and Effectors: Lessons Learned from Animal Models

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