Transient transfection of mouse fibroblasts with type I interferon transgenes provides various degrees of protection against herpes simplex virus infection

Härle, Peter; Cull, Vanessa S.; Guo, Lan; Papin, James F.; Lawson, Cassandra M.; Carr, Daniel J.J.

doi:10.1016/s0166-3542(02)00093-1

Cited by 24 publications

(22 citation statements)

References 35 publications

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“…Mice deficient in the A1 chain of the type I IFN receptor are not able to respond to the ligands IFN-␣ and IFN-␤, two potent antiviral cytokines that suppress HSV-2 replication (25). As a consequence, unabated viral replication occurs and the virus can disseminate locally and by retrograde transport to sites proximal and distal to the portal of entry.…”

Section: Discussionmentioning

confidence: 99%

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Loss of the Type I Interferon Pathway Increases Vulnerability of Mice to Genital Herpes Simplex Virus 2 Infection

Conrady

Halford

Carr

2011

J Virol

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The mouse model of genital herpes relies on medoxyprogesterone treatment of female mice to render the vaginal lumen susceptible to inoculation with herpes simplex virus 2 (HSV-2). In the present study, we report that mice deficient in the A1 chain of the type I interferon receptor (CD118 ؊/؊ ) are susceptible to HSV-2 in the absence of medroxyprogesterone preconditioning. In the absence of hormone pretreatment, 2,000 PFU of a clinical isolate of HSV-2 was sufficient to establish a productive infection in the vagina of 75% ؎ 17% and in the spinal cord of 71% ؎ 14% of CD118 ؊/؊ mice, whereas the same dose of HSV-2 replicated to detectable levels in only 13% ؎ 13% of vaginal samples and 0% of spinal cord samples from wild-type mice, as determined at day 5 postinfection. The susceptibility to HSV-2 infection in the CD118 ؊/؊ mice was associated with a significant reduction in the infiltration of HSV-specific cytotoxic T lymphocytes into the vaginal tissue, the local production of gamma interferon (IFN-␥), and the expression of T cell-recruiting chemokines CCL5, CXCL9, and CXCL10. Collectively, the results underscore the significant contribution of type I IFNs in resistance to genital HSV-2 infection.

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Section: Discussionmentioning

confidence: 99%

“…Supernatants were clarified by centrifugation (10,000 ϫ g, 1 min). The clarified supernatants were assayed for viral content by plaque assay (25). The results are reported as log PFU/tissue.…”

Section: Cells and Virusmentioning

confidence: 99%

Loss of the Type I Interferon Pathway Increases Vulnerability of Mice to Genital Herpes Simplex Virus 2 Infection

Conrady

Halford

Carr

2011

J Virol

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“…Some experimental data support the hypothesis that the IFN-␣ genes might exert qualitatively distinct biological functions. For instance, Harle et al recently showed that IFN-␣/␤ subtypes differed in their antiviral potencies against two herpes simplex virus strains (19).…”

mentioning

confidence: 99%

Characterization of the Murine Alpha Interferon Gene Family

Pesch

Lanaya

Renauld

et al. 2004

J Virol

176

156

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Mouse and human genomes carry more than a dozen genes coding for closely related alpha interferon (IFN-␣) subtypes. IFN-␣, as well as IFN-␤, IFN-, IFN-, and limitin, are thought to bind the same receptor, raising the question of whether different IFN subtypes possess specific functions. As some confusion existed in the identity and characteristics of mouse IFN-␣ subtypes, the availability of data from the mouse genome sequence prompted us to characterize the murine IFN-␣ family. A total of 14 IFN-␣ genes were detected in the mouse genome, in addition to three IFN-␣ pseudogenes. Four IFN-␣ genes (IFN-␣1, IFN-␣7/10, IFN-␣8/6, and IFN-␣11) exhibited surprising allelic divergence between 129/Sv and C57BL/6 mice. All IFN-␣ subtypes were found to be stable at pH 2 and to exhibit antiviral activity. Interestingly, some IFN subtypes (IFN-␣4, IFN-␣11, IFN-␣12, IFN-␤, and limitin) showed higher biological activity levels than others, whereas IFN-␣7/10 exhibited lower activity. Most murine IFN-␣ turned out to be N-glycosylated. However, no correlation was found between N-glycosylation and activity. The various IFN-␣ subtypes displayed a good correlation between their antiviral and antiproliferative potencies, suggesting that IFN-␣ subtypes did not diverge primarily to acquire specific biological activities but probably evolved to acquire specific expression patterns. In L929 cells, IFN genes activated in response to poly(I•C) transfection or to viral infection were, however, similar.

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“…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]. In vitro, IFN−β was also superior to the IFN−αs against HSV-1 infection with greater reduction of viral gene expression [79]. The downstream mechanisms of IFN regulation of HSV replication are not fully understood, although several IFN-induced pathways have been investigated.…”

Section: Ifns and Hsvsmentioning

confidence: 94%

“…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: 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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Transient transfection of mouse fibroblasts with type I interferon transgenes provides various degrees of protection against herpes simplex virus infection

Cited by 24 publications

References 35 publications

Loss of the Type I Interferon Pathway Increases Vulnerability of Mice to Genital Herpes Simplex Virus 2 Infection

Loss of the Type I Interferon Pathway Increases Vulnerability of Mice to Genital Herpes Simplex Virus 2 Infection

Characterization of the Murine Alpha Interferon Gene Family

Interferons as Biomarkers and Effectors: Lessons Learned from Animal Models

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