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The constant exposure of ocular surface to external environment and then to several microbial agents is often related to the pathogenesis of various inflammatory eye disorders. In the present study α-Smooth Muscle Actin (α-SMA) and Langerin CD/207 expression and function was investigated in a rabbit corneal keratitis. The inflammation was induced by the secreted form of glycoprotein B (gB1s) of HSV-1, in an ex vivo rabbit corneal model. α-SMA is often used as a marker for myofibroblasts. In this study, for the first time, we show α-SMA positive corneal epithelial cells, during HSV-1 cornea inflammation, demonstrating a crucial role in wound healing, especially during remodeling phase. Furthermore, we show the presence of Dendritic Cells Langerin CD/207 positive, located mainly in the basal epithelial layer and in corneal stroma during the inflammatory processes. Our result validating the ex vivo organotypic rabbit corneal model, for the study about pathogenesis of HSV-1 ocular infection.

One goal of neuroscience is to define the molecular and cellular basis for behavior and neurological diseases. A novel approach to this problem is based on the use of viral vectors to transfect specific genes into specific brain cell populations. This review focuses on herpes simplex-based vectors. Major advances have recently been made to improve the characteristics of these vectors, in particular to reduce their toxicity, to modulate the greatness and the time-course of transgene expression, to precisely target specific cell populations, and to transfer multiple genes. Much remains to be done to obtain robust and prolonged transgene expression. However, specific alterations in the behavior and in disease models have already been described following the herpes simplex vector-mediated expression of specific genes within highly localized brain areas. Therefore, this research strategy is likely to provide new clues on the cellular and molecular basis of behavior and of neurological diseases.

In this report, a replication-defective herpes simplex virus type 1 (HSV-1) vector has been employed to deliver the Escherichia coli LacZ and HSV thymidine kinase (HSVtk) genes to six human ovarian carcinoma cell lines and the efficacy of gene transfer compared to that of adenoviral vectors in vitro. The transduction efficiency of the LacZ-containing virus TOZ.1 was evaluated qualitatively and quantitatively following infection of the different ovarian cancer cell lines. The therapeutic ability of the HSV-T3 vector, which contains the HSVtk gene, was additionally investigated in comparison to the AdCMVHSVTK. Our results show that HSV-1-mediated gene transfer is quantitatively superior to adenoviral vector in five of the six ovarian cancer cell lines at a 100-fold lower dose in vitro. Our preliminary studies suggest that HSV-1 may be a promising alternative vector for ovarian cancer gene therapy.

Different viral vectors have been analyzed as gene delivery vehicles to skeletal muscle for potentially therapeutic purposes. In this review, we evaluate the application of retroviral, adenoviral, and herpes simplex viral vectors to deliver genes to skeletal muscle and focus on the dramatic loss of viral transduction detected throughout muscle maturation. Recent results suggested that there are several factors involved in the reduced viral transducibility of mature skeletal muscle: muscle cells become post-mitotic in an early stage, the extracellular matrix develops into a physical barrier, and a loss of myoblast mediation occurs since myoblasts progressively become quiescent. Approaches to improve viral gene delivery to mature skeletal muscle may include the use of particular enzymes to increase the permeability of the extracellular matrix, the pre-treatment of the muscle with a myonecrotic agent to induce myoblast mediation, or the application of the myoblast-mediated ex vivo gene transfer.

In this report the ability of enteric immunization with recombinant replication deficient (ICP4-/-) HSV expressing IFN gamma to generate protection and modulate mucosal and systemic immunity was evaluated. ICP4-/-HSV, ICP4-/-HSV expressing IL4, live replicating, and uv HSV were used as controls. Following enteric administration of live HSV, a Th1 cytokine response was induced in the spleen, while both Th1 and notable Th2 cytokine production were detected at mucosal sites. Modulation of mucosal and systemic immune response was achieved when nonreplicating recombinant HSV viruses expressing cytokines were used. Compared to the control replication defective viruses, decreased frequency of Th2 cytokine producing cells in Peyer's patches was observed following enteric administration of nonreplicating HSV expressing IFN gamma. When IFN gamma expressing virus was given enterically, modulation was observed at the systemic level, measured by ELISPOT for cytokine producing cells, ELISA from the in vitro restimulated splenic cell cultures, and by the increase of the IgG2a/IgG1 ratio in the serum. This report provides evidence that replication defective viruses expressing cytokine genes in contrast to uv HSV, are immunogenic when administered enterically and can generate significant immunomodulatory effects at the mucosal and systemic levels.