Date of Award

Summer 2013

Degree Type

Masters Thesis

Degree Name

Master of Science (MS)

Department

Biological Sciences

Committee Chair

Yanlin Guo

Committee Chair Department

Biological Sciences

Committee Member 2

Faqing Huang

Committee Member 2 Department

Chemistry and Biochemistry

Committee Member 3

Fengwei Bai

Committee Member 3 Department

Biological Sciences

Abstract

Embryonic stem cells (ESCs) are cells that have unlimited capacity for selfrenewal and differentiation. These properties make ESCs a great cell source for application in regenerative medicine. When used for cell therapy, ESC-derived cells could be placed in a wounded area that is likely to be exposed to various pathogens. However, it is not well-understood whether ESCs and ESC-derived cells have active antiviral responses against infectious agents from the environment. To answer this important question, I comparatively analyzed the antiviral responses of ESCs and mesenchymal stem cells (MSCs, C3H10Tl/2 cell line) to infectious agents. Using the expression of type I interferon (IFN) as a benchmark of antiviral responses, our results indicated that the type I IFN were robustly induced in C3Hl0Tl/2 cells, but not in ESCs, when they were exposed to polyinosinic:polycytidylic acid (poly(I:C), a dsRNA viral analog) and La Crosse Virus (LACV). Our results also showed that TLR3, RIG! and MDA5, the receptors for viral RNA, are expressed at lower levels in mouse ESCs (mESCs) than in C3H10Tl/2 cells. However, mESCs are susceptible to LACV infection resulting in cell death, which can be reduced by IFNP pretreatment. Furthermore, IFNP induced expression of ISG 15, PKR and dsRNA receptor genes that play key roles in antiviral responses. In conclusion, mESCs are deficient in type I IFN expression, but they have functional mechanisms that mediate the antiviral effects of type I IFN.

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