HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Higaki, S. Articles by Hill, J. M. Search for Related Content PubMed PubMed Citation Articles by Higaki, S. Articles by Hill, J. M.

Effect of Immunosuppression on Gene Expression in the HSV-1 Latently Infected Mouse Trigeminal Ganglion

¹ From the Department of Ophthalmology, LSU Eye Center, New Orleans, Louisiana; the ² Department of Microbiology, the ³ Neuroscience Center, and the ⁴ Department of Pharmacology, Louisiana State University Health Sciences Center at New Orleans, New Orleans, Louisiana.

PURPOSE. To determine alterations in expression of genes in herpes simples virus (HSV)-1 latently infected mouse trigeminal ganglia (TGs), after treatment with cyclophosphamide and dexamethasone.

METHODS. Scarified corneas of female BALB/c mice were inoculated with HSV-1 strain McKrae. Four weeks after inoculation, cyclophosphamide and dexamethasone were intravenously injected to induce HSV-1 reactivation. Uninfected mice were also treated with the immunosuppressants. Four groups of animals were studied: uninfected, not treated; uninfected, drug treated; latently infected, not treated; and latently infected, drug treated. PolyA⁺ mRNA from the TGs of each group was reverse transcribed, labeled with ³²P, incubated on a 1185-gene array membrane, and analyzed by phosphorimaging. As a comparison and to confirm microarray results, semiquantitative RT-PCR was also performed for selected genes.

RESULTS. The immunosuppressive drugs significantly increased expression of two genes (calpactin 1 light chain and guanine nucleotide-binding protein –stimulating polypeptide [GNAS]) in the ganglia of uninfected mice compared with those in untreated uninfected mice. Ten genes were shown to be significantly increased in the latent TGs of mice treated with immunosuppressants compared with latently infected untreated mice. These genes were prostaglandin E₂ receptor EP4 subtype (PTGER4), insulin promoter factor 1 (IPF1), glutathione S-transferase µ2, cyclin D2, peripherin, plasma glutathione peroxidase, methyl CpG-binding protein 2, retinal S-antigen, ErbB2 proto-oncogene, and GNAS. Eight genes were shown to be significantly decreased in the HSV-1 latent TGs treated with the drugs, compared with untreated latently infected mice. These genes were peripheral myelin protein 22, decorin, transcription factor AP-1, dystroglycan 1, myelin protein zero, mitogen-activated protein kinase 3, prothymosin beta 4, and brain lipid-binding protein. The results obtained by semiquantitative RT-PCR were similar to those obtained by microarray analysis.

CONCLUSIONS. Those genes with expression altered by immunosuppressive drug treatment may play an important role in ocular HSV-1 recurrence. Changes in expression of genes in the prostaglandin pathway, a transcription factor, and an enzyme in the cell cycle are considered especially important in HSV-1 reactivation by immunosuppression and are reviewed.

This article has been cited by other articles:

				C. Clement, P. S. Bhattacharjee, H. E. Kaufman, and J. M. Hill Heat-Induced Reactivation of HSV-1 in Latent Mice: Upregulation in the TG of CD83 and Other Immune Response Genes and Their LAT-ICP0 Locus Invest. Ophthalmol. Vis. Sci., June 1, 2009; 50(6): 2855 - 2861. [Abstract] [Full Text] [PDF]

				D. Stapler, E. D. Lee, S. A. Selvaraj, A. G. Evans, L. S. Kean, S. H. Speck, C. P. Larsen, and S. Gangappa Expansion of Effector Memory TCR V{beta}4+CD8+ T Cells Is Associated with Latent Infection-Mediated Resistance to Transplantation Tolerance J. Immunol., March 1, 2008; 180(5): 3190 - 3200. [Abstract] [Full Text] [PDF]

				D. M. Neumann, P. S. Bhattacharjee, and J. M. Hill Sodium Butyrate: a Chemical Inducer of In Vivo Reactivation of Herpes Simplex Virus Type 1 in the Ocular Mouse Model J. Virol., June 1, 2007; 81(11): 6106 - 6110. [Abstract] [Full Text] [PDF]

				T. J. Pasieka, T. Baas, V. S. Carter, S. C. Proll, M. G. Katze, and D. A. Leib Functional genomic analysis of herpes simplex virus type 1 counteraction of the host innate response. J. Virol., August 1, 2006; 80(15): 7600 - 7612. [Abstract] [Full Text] [PDF]

				O. Saydam, C. Abril, B. Vogt, M. Ackermann, and M. Schwyzer Transactivator Protein BICP0 of Bovine Herpesvirus 1 (BHV-1) Is Blocked by Prostaglandin D2 (PGD2), Which Points to a Mechanism for PGD2-Mediated Inhibition of BHV-1 Replication J. Virol., April 15, 2004; 78(8): 3805 - 3810. [Abstract] [Full Text] [PDF]

				R. J. Cohrs, M. P. Hurley, and D. H. Gilden Array Analysis of Viral Gene Transcription during Lytic Infection of Cells in Tissue Culture with Varicella-Zoster Virus J. Virol., November 1, 2003; 77(21): 11718 - 11732. [Abstract] [Full Text] [PDF]