Microarray analysis of host gene expression for comparison between naïve and HSV-1 latent rabbit trigeminal ganglia

Christian Clement, Michael P. Popp, David C. Bloom, Gregory Schultz, Li Liu, Donna M. Neumann, Partha S. Bhattachrjee, James M. Hill

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Purpose: To analyze the rabbit host global gene expression patterns in uninfected and herpes simplex virus type 1 (HSV-1) latent trigeminal ganglia (TG) for identification of host response-initiated transcriptional changes during the maintenance of viral latency. Methods: The corneas of eight-week-old New Zealand White rabbits were scarified and inoculated with HSV-1 strain McKrae, 5×105 plaque forming units/eye. Corneal infection was verified by slit-lamp examination. Prior to sacrifice at 30 days post infection, ocular swabs confirmed no infectious virus was present. TG were aseptically removed from rabbits and placed in RNA stabilization solution. Host RNA was isolated from two groups of TG, uninfected and HSV-1 latent infected, and used to create labeled cRNA. Labeled cRNA was hybridized to two new and novel custom oligonucleotide rabbit arrays, containing a total of 3,123 probes for rabbit genes. Results: The rabbit TG expressed approximately 80% of genes out of a total of 3,123. A one-way ANOVA performed on the log2 transformed signal ratios showed 611 genes were significantly altered (p≤0.05) in HSV-1 latent TG. These genes, if annotated, were separated by biologic process categories. Five broad categories were most heavily represented: protein processing, carbohydrate processing, cell adhesion, apoptosis, and host defense and immune response. Sixty of the significantly altered genes were found to be altered by more than 2 fold, and five were altered by more than 4 fold. The genes altered by more than 4 fold were all upregulated and related to host defense and immune response. Viral latency had a large effect on protein processing. Of the differentially expressed genes with an assigned biologic process, 90/349 (25.7%) were associated with protein processing. The next most populated categories were carbohydrate metabolism 39/349 (11.1%) and host defense and immune response 17/349 (4.9%). Conclusions: The results of this microarray study demonstrate that host gene expression is altered in the HSV-1 latent rabbit TG. The shift in molecular processes at a pathway level reveals the presence of potential therapeutic significance inherent in the maintenance of HSV-1 latency. This is the first large-scale rabbit gene expression study, using microarray analysis, that documents the involvement of host immunity in maintaining HSV-1 latency.

Original languageEnglish (US)
Pages (from-to)1209-1221
Number of pages13
JournalMolecular Vision
Volume14
StatePublished - Jul 3 2008
Externally publishedYes

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Trigeminal Ganglion
Human Herpesvirus 1
Microarray Analysis
Virus Latency
Rabbits
Gene Expression
Genes
Complementary RNA
Maintenance
RNA
Eye Infections
Proteins
Carbohydrate Metabolism
Oligonucleotide Array Sequence Analysis
Cell Adhesion
Cornea
Immunity
Analysis of Variance
Carbohydrates
Apoptosis

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Clement, C., Popp, M. P., Bloom, D. C., Schultz, G., Liu, L., Neumann, D. M., ... Hill, J. M. (2008). Microarray analysis of host gene expression for comparison between naïve and HSV-1 latent rabbit trigeminal ganglia. Molecular Vision, 14, 1209-1221.

Microarray analysis of host gene expression for comparison between naïve and HSV-1 latent rabbit trigeminal ganglia. / Clement, Christian; Popp, Michael P.; Bloom, David C.; Schultz, Gregory; Liu, Li; Neumann, Donna M.; Bhattachrjee, Partha S.; Hill, James M.

In: Molecular Vision, Vol. 14, 03.07.2008, p. 1209-1221.

Research output: Contribution to journalArticle

Clement, C, Popp, MP, Bloom, DC, Schultz, G, Liu, L, Neumann, DM, Bhattachrjee, PS & Hill, JM 2008, 'Microarray analysis of host gene expression for comparison between naïve and HSV-1 latent rabbit trigeminal ganglia', Molecular Vision, vol. 14, pp. 1209-1221.
Clement, Christian ; Popp, Michael P. ; Bloom, David C. ; Schultz, Gregory ; Liu, Li ; Neumann, Donna M. ; Bhattachrjee, Partha S. ; Hill, James M. / Microarray analysis of host gene expression for comparison between naïve and HSV-1 latent rabbit trigeminal ganglia. In: Molecular Vision. 2008 ; Vol. 14. pp. 1209-1221.
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abstract = "Purpose: To analyze the rabbit host global gene expression patterns in uninfected and herpes simplex virus type 1 (HSV-1) latent trigeminal ganglia (TG) for identification of host response-initiated transcriptional changes during the maintenance of viral latency. Methods: The corneas of eight-week-old New Zealand White rabbits were scarified and inoculated with HSV-1 strain McKrae, 5×105 plaque forming units/eye. Corneal infection was verified by slit-lamp examination. Prior to sacrifice at 30 days post infection, ocular swabs confirmed no infectious virus was present. TG were aseptically removed from rabbits and placed in RNA stabilization solution. Host RNA was isolated from two groups of TG, uninfected and HSV-1 latent infected, and used to create labeled cRNA. Labeled cRNA was hybridized to two new and novel custom oligonucleotide rabbit arrays, containing a total of 3,123 probes for rabbit genes. Results: The rabbit TG expressed approximately 80{\%} of genes out of a total of 3,123. A one-way ANOVA performed on the log2 transformed signal ratios showed 611 genes were significantly altered (p≤0.05) in HSV-1 latent TG. These genes, if annotated, were separated by biologic process categories. Five broad categories were most heavily represented: protein processing, carbohydrate processing, cell adhesion, apoptosis, and host defense and immune response. Sixty of the significantly altered genes were found to be altered by more than 2 fold, and five were altered by more than 4 fold. The genes altered by more than 4 fold were all upregulated and related to host defense and immune response. Viral latency had a large effect on protein processing. Of the differentially expressed genes with an assigned biologic process, 90/349 (25.7{\%}) were associated with protein processing. The next most populated categories were carbohydrate metabolism 39/349 (11.1{\%}) and host defense and immune response 17/349 (4.9{\%}). Conclusions: The results of this microarray study demonstrate that host gene expression is altered in the HSV-1 latent rabbit TG. The shift in molecular processes at a pathway level reveals the presence of potential therapeutic significance inherent in the maintenance of HSV-1 latency. This is the first large-scale rabbit gene expression study, using microarray analysis, that documents the involvement of host immunity in maintaining HSV-1 latency.",
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AU - Clement, Christian

AU - Popp, Michael P.

AU - Bloom, David C.

AU - Schultz, Gregory

AU - Liu, Li

AU - Neumann, Donna M.

AU - Bhattachrjee, Partha S.

AU - Hill, James M.

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N2 - Purpose: To analyze the rabbit host global gene expression patterns in uninfected and herpes simplex virus type 1 (HSV-1) latent trigeminal ganglia (TG) for identification of host response-initiated transcriptional changes during the maintenance of viral latency. Methods: The corneas of eight-week-old New Zealand White rabbits were scarified and inoculated with HSV-1 strain McKrae, 5×105 plaque forming units/eye. Corneal infection was verified by slit-lamp examination. Prior to sacrifice at 30 days post infection, ocular swabs confirmed no infectious virus was present. TG were aseptically removed from rabbits and placed in RNA stabilization solution. Host RNA was isolated from two groups of TG, uninfected and HSV-1 latent infected, and used to create labeled cRNA. Labeled cRNA was hybridized to two new and novel custom oligonucleotide rabbit arrays, containing a total of 3,123 probes for rabbit genes. Results: The rabbit TG expressed approximately 80% of genes out of a total of 3,123. A one-way ANOVA performed on the log2 transformed signal ratios showed 611 genes were significantly altered (p≤0.05) in HSV-1 latent TG. These genes, if annotated, were separated by biologic process categories. Five broad categories were most heavily represented: protein processing, carbohydrate processing, cell adhesion, apoptosis, and host defense and immune response. Sixty of the significantly altered genes were found to be altered by more than 2 fold, and five were altered by more than 4 fold. The genes altered by more than 4 fold were all upregulated and related to host defense and immune response. Viral latency had a large effect on protein processing. Of the differentially expressed genes with an assigned biologic process, 90/349 (25.7%) were associated with protein processing. The next most populated categories were carbohydrate metabolism 39/349 (11.1%) and host defense and immune response 17/349 (4.9%). Conclusions: The results of this microarray study demonstrate that host gene expression is altered in the HSV-1 latent rabbit TG. The shift in molecular processes at a pathway level reveals the presence of potential therapeutic significance inherent in the maintenance of HSV-1 latency. This is the first large-scale rabbit gene expression study, using microarray analysis, that documents the involvement of host immunity in maintaining HSV-1 latency.

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