Infection of ENU Mutant Mice With Human Herpes Simplex Virus-1 (HSV-1) to Probe Immune Deviations in the Host Predominantly Expressing IL-15 Splice Variants
Date Issued
2008
Date
2008
Author(s)
Yang, Fu-Ju
Abstract
Interlukine-15 (IL-15) is one of important cytokines and exhibits a high degree of pleiotropy, controlling a wide range of functions including immune responses, metabolism of skeletal muscle and proliferation of keratinocytes. However, very little is known about the mechanisms by which the expression and bioactivity of IL-15 are controlled. Whereas several forms of IL-15 alternative splice variants are identified in normal mice, their roles in the control of IL-15 expression remain unclear. In this study, we used an ENU mutant mouse model generated by the MMPCF (Mouse Mutagenesis Program Core Facility) to investigate how the immune responses against virus infection are affected when the host predominantly expresses IL-15 splice variants. Normal C57BL/6 (B6) and mutant pedigree 191 (P191) were infected with Human Herpes Simplex Virus-1 (HSV-1) via epicutanous route. Skin samples with lesional areas were collected and sectioned for further analysis. Results from H & E stain showed that HSV-1 induced typical pathological changes in skin tissues of both types of mice including cell ballooning, vesicular degeneration and epidermal cytolysis. However, these changes appeared earlier and more severe in P191 than in wild type B6 skin. Expression of HSV-1 proteins was also more abundant in P191 than in B6 skin by immunohistochemical stain. Whereas expressions of IL-15 and IL-15R were induced in the subdermal area of B6 skin after HSV-1 infection, they were much reduced in P191 lesional skin. In addition, the time for the skin to be healed after HSV-1 infection was longer for P191 than B6 mice. While significant numbers of Gr-1+ cells were detected on day 5 and peaked at day 10 in the dermis of infected B6 skin, they were nearly detected at all times in P191 skin after HSV-1 infection. Although CD3+ T cells were all detected in B6 and P191 skin after HSV-1 infection, their roles in the control of virus infection remain clarified. In summary, results from our study have shown that infection of P191 mice with HSV-1 resulted in altered immune responses as compared with wild type B6 mice. The differences at least but not limited include the susceptibility to HSV-1 infection, time for skin healing and recruitment of immune cells to lesional areas. How does the elevated level of IL-15 splice variants in P191 mice contribute to these deviations is not clear. More experiments will be done to understand whether IL-15 splice variants are expressed as variant proteins to antagonize prototype IL-15 and/or acquire novel functions in regulating host immune responses.
Subjects
Interleukin-15
Splice Variants
Human Herpes Simplex Virus-1
ENU Mutant Mice
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